Available systemic treatment options for cancers of the genitourinary system have experienced great progress in the last decade. However, a large proportion of patients eventually develop resistance to treatment, resulting in disease progression and shorter overall survival. Biomarkers indicating the increasing resistance to cancer therapies are yet to enter clinical routine. Long non-coding RNAs (lncRNA) are non-protein coding RNA transcripts longer than 200 nucleotides that exert multiple types of regulatory functions of all known cellular processes. Increasing evidence supports the role of lncRNAs in cancer development and progression. Additionally, their involvement in the development of drug resistance across various cancer entities, including genitourinary malignancies, are starting to be discovered. Consequently, lncRNAs have been suggested as factors in novel therapeutic strategies to overcome drug resistance in cancer. In this review, the existing evidences on lncRNAs and their involvement in mechanisms of drug resistance in cancers of the genitourinary system, including renal cell carcinoma, bladder cancer, prostate cancer, and testicular cancer, will be highlighted and discussed to facilitate and encourage further research in this field. We summarize a significant number of lncRNAs with proposed pathways in drug resistance and available reported studies.

Central European Institute of Technology Masaryk University 62500 Brno Czech Republic

Department of Comprehensive Cancer Care Masaryk Memorial Cancer Institute 62500 Brno Czech Republic

Department of Experimental Therapeutics The University of Texas MD Anderson Cancer Center Houston TX 77030 USA

Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer Center Houston TX 77030 USA

Research Unit of Non Coding RNAs and Genome Editing in Cancer Division of Clinical Oncology Department of Medicine Comprehensive Cancer Center Graz Medical University of Graz 8036 Graz Austria

Zobrazit více v PubMed

Ferlay J., Soerjomataram I., Dikshit R., Eser S., Mathers C., Rebelo M., Parkin D.M., Forman D., Bray F. Cancer Incidence and Mortality Worldwide: Sources, Methods and Major Patterns in GLOBOCAN 2012. Int. J. Cancer. 2015;136:E359–E386. doi: 10.1002/ijc.29210. PubMed DOI

Suarez C., Puente J., Gallardo E., Mendez-Vidal M.J., Climent M.A., Leon L., Olmos D., Garcia del Muro X., Gonzalez-Billalabeitia E., Grande E., et al. New Advances in Genitourinary Cancer: Evidence Gathered in 2014. Cancer Metastasis Rev. 2015;34:443–464. doi: 10.1007/s10555-015-9577-x. PubMed DOI

Beer T.M., Armstrong A.J., Rathkopf D.E., Loriot Y., Sternberg C.N., Higano C.S., Iversen P., Bhattacharya S., Carles J., Chowdhury S., et al. Enzalutamide in Metastatic Prostate Cancer before Chemotherapy. N. Engl. J. Med. 2014;371:424–433. doi: 10.1056/NEJMoa1405095. PubMed DOI PMC

Bellmunt J., de Wit R., Vaughn D.J., Fradet Y., Lee J.L., Fong L., Vogelzang N.J., Climent M.A., Petrylak D.P., Choueiri T.K., et al. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N. Engl. J. Med. 2017;376:1015–1026. doi: 10.1056/NEJMoa1613683. PubMed DOI PMC

Motzer R.J., Tannir N.M., McDermott D.F., Aren Frontera O., Melichar B., Choueiri T.K., Plimack E.R., Barthelemy P., Porta C., George S., et al. Nivolumab Plus Ipilimumab Versus Sunitinib in Advanced Renal-Cell Carcinoma. N. Engl. J. Med. 2018;378:1277–1290. doi: 10.1056/NEJMoa1712126. PubMed DOI PMC

Garcia-Mayea Y., Mir C., Masson F., Paciucci R., LLeonart M.E. Insights into New Mechanisms and Models of Cancer Stem Cell Multidrug Resistance. Semin. Cancer Biol. 2020;60:166–180. doi: 10.1016/j.semcancer.2019.07.022. PubMed DOI

Seles M., Hutterer G.C., Fosselteder J., Svoboda M., Resel M., Barth D.A., Pichler R., Bauernhofer T., Zigeuner R.E., Pummer K., et al. Long Non-Coding RNA PANTR1 is Associated with Poor Prognosis and Influences Angiogenesis and Apoptosis in Clear-Cell Renal Cell Cancer. Cancers. 2020;12:1200. doi: 10.3390/cancers12051200. PubMed DOI PMC

Pichler M., Rodriguez-Aguayo C., Nam S.Y., Dragomir M.P., Bayraktar R., Anfossi S., Knutsen E., Ivan C., Fuentes-Mattei E., Lee S.K., et al. Therapeutic Potential of FLANC, a Novel Primate-Specific Long Non-Coding RNA in Colorectal Cancer. Gut. 2020 doi: 10.1136/gutjnl-2019-318903. PubMed DOI PMC

Shah M.Y., Ferracin M., Pileczki V., Chen B., Redis R., Fabris L., Zhang X., Ivan C., Shimizu M., Rodriguez-Aguayo C., et al. Cancer-Associated rs6983267 SNP and its Accompanying Long Noncoding RNA CCAT2 Induce Myeloid Malignancies Via Unique SNP-Specific RNA Mutations. Genome Res. 2018;28:432–447. doi: 10.1101/gr.225128.117. PubMed DOI PMC

Fabbri M., Girnita L., Varani G., Calin G.A. Decrypting Noncoding RNA Interactions, Structures, and Functional Networks. Genome Res. 2019;29:1377–1388. doi: 10.1101/gr.247239.118. PubMed DOI PMC

Rigoutsos I., Lee S.K., Nam S.Y., Anfossi S., Pasculli B., Pichler M., Jing Y., Rodriguez-Aguayo C., Telonis A.G., Rossi S., et al. N-BLR, a Primate-Specific Non-Coding Transcript Leads to Colorectal Cancer Invasion and Migration. Genome Biol. 2017;18:98. doi: 10.1186/s13059-017-1224-0. PubMed DOI PMC

Ma L., Bajic V.B., Zhang Z. On the Classification of Long Non-Coding RNAs. RNA Biol. 2013;10:925–933. doi: 10.4161/rna.24604. PubMed DOI PMC

Wang K., Chang H. Molecular Mechanisms of Long Noncoding RNAs. Mol. Cell. 2011;43:904–914. doi: 10.1016/j.molcel.2011.08.018. PubMed DOI PMC

Martens-Uzunova E.S., Bottcher R., Croce C.M., Jenster G., Visakorpi T., Calin G.A. Long Noncoding RNA in Prostate, Bladder, and Kidney Cancer. Eur. Urol. 2014;65:1140–1151. doi: 10.1016/j.eururo.2013.12.003. PubMed DOI

Xu Z., Yang F., Wei D., Liu B., Chen C., Bao Y., Wu Z., Wu D., Tan H., Li J., et al. Long Noncoding RNA-SRLR Elicits Intrinsic Sorafenib Resistance Via Evoking IL-6/STAT3 Axis in Renal Cell Carcinoma. Oncogene. 2017;36:1965–1977. doi: 10.1038/onc.2016.356. PubMed DOI

Qu L., Ding J., Chen C., Wu Z.J., Liu B., Gao Y., Chen W., Liu F., Sun W., Li X.F., et al. Exosome-Transmitted lncARSR Promotes Sunitinib Resistance in Renal Cancer by Acting as a Competing Endogenous RNA. Cancer Cell. 2016;29:653–668. doi: 10.1016/j.ccell.2016.03.004. PubMed DOI

Song E.L., Xing L., Wang L., Song W.T., Li D.B., Wang Y., Gu Y.W., Liu M.M., Ni W.J., Zhang P., et al. LncRNA ADAMTS9-AS2 Inhibits Cell Proliferation and Decreases Chemoresistance in Clear Cell Renal Cell Carcinoma Via the miR-27a-3p/FOXO1 Axis. Aging Albany NY. 2019;11:5705–5725. doi: 10.18632/aging.102154. PubMed DOI PMC

Liu F., Chen N., Gong Y., Xiao R., Wang W., Pan Z. The Long Non-Coding RNA NEAT1 Enhances Epithelial-to-Mesenchymal Transition and Chemoresistance Via the miR-34a/C-Met Axis in Renal Cell Carcinoma. Oncotarget. 2017;8:62927–62938. doi: 10.18632/oncotarget.17757. PubMed DOI PMC

Liu L., Pang X., Shang W., Xie H., Feng Y., Feng G. Long Non-Coding RNA GAS5 Sensitizes Renal Cell Carcinoma to Sorafenib Via miR-21/SOX5 Pathway. Cell. Cycle. 2019;18:257–263. doi: 10.1080/15384101.2018.1475826. PubMed DOI PMC

Pan J., Li X., Wu W., Xue M., Hou H., Zhai W., Chen W. Long Non-Coding RNA UCA1 Promotes Cisplatin/Gemcitabine Resistance through CREB Modulating miR-196a-5p in Bladder Cancer Cells. Cancer Lett. 2016;382:64–76. doi: 10.1016/j.canlet.2016.08.015. PubMed DOI

Fan Y., Shen B., Tan M., Mu X., Qin Y., Zhang F., Liu Y. Long Non-Coding RNA UCA1 Increases Chemoresistance of Bladder Cancer Cells by Regulating Wnt Signaling. FEBS J. 2014;281:1750–1758. doi: 10.1111/febs.12737. PubMed DOI

Wu J., Li W., Ning J., Yu W., Rao T., Cheng F. Long Noncoding RNA UCA1 Targets miR-582-5p and Contributes to the Progression and Drug Resistance of Bladder Cancer Cells through ATG7-Mediated Autophagy Inhibition. Onco Targets Ther. 2019;12:495–508. doi: 10.2147/OTT.S183940. PubMed DOI PMC

Yu G., Zhou H., Yao W., Meng L., Lang B. lncRNA TUG1 Promotes Cisplatin Resistance by Regulating CCND2 Via Epigenetically Silencing miR-194-5p in Bladder Cancer. Mol. Ther. Nucleic Acids. 2019;16:257–271. doi: 10.1016/j.omtn.2019.02.017. PubMed DOI PMC

Liu Z., Zhang H. LncRNA Plasmacytoma Variant Translocation 1 is an Oncogene in Bladder Urothelial Carcinoma. Oncotarget. 2017;8:64273–64282. doi: 10.18632/oncotarget.19604. PubMed DOI PMC

An Q., Zhou L., Xu N. Long Noncoding RNA FOXD2-AS1 Accelerates the Gemcitabine-Resistance of Bladder Cancer by Sponging miR-143. Biomed. Pharmacother. 2018;103:415–420. doi: 10.1016/j.biopha.2018.03.138. PubMed DOI

Li Y., Shi B., Dong F., Zhu X., Liu B., Liu Y. Long Non-Coding RNA DLEU1 Promotes Cell Proliferation, Invasion, and Confers Cisplatin Resistance in Bladder Cancer by Regulating the miR-99b/HS3ST3B1 Axis. Front. Genet. 2019;10:280. doi: 10.3389/fgene.2019.00280. PubMed DOI PMC

Chen J., Li Y., Li Z., Cao L. LncRNA MST1P2/miR-133b Axis Affects the Chemoresistance of Bladder Cancer to Cisplatin-Based Therapy Via Sirt1/p53 Signaling. J. Biochem. Mol. Toxicol. 2020;34:e22452. doi: 10.1002/jbt.22452. PubMed DOI

Chen X., Liu M., Meng F., Sun B., Jin X., Jia C. The Long Noncoding RNA HIF1A-AS2 Facilitates Cisplatin Resistance in Bladder Cancer. J. Cell. Biochem. 2019;120:243–252. doi: 10.1002/jcb.27327. PubMed DOI

Li B., Xie D., Zhang H. Long Non-Coding RNA GHET1 Contributes to Chemotherapeutic Resistance to Gemcitabine in Bladder Cancer. Cancer Chemother. Pharmacol. 2019;84:187–194. doi: 10.1007/s00280-019-03873-8. PubMed DOI

Liu P., Li X., Cui Y., Chen J., Li C., Li Q., Li H., Zhang X., Zu X. LncRNA-MALAT1 Mediates Cisplatin Resistance Via miR-101-3p/VEGF-C Pathway in Bladder Cancer. Acta Biochim. Biophys. Sin. Shanghai. 2019;51:1148–1157. doi: 10.1093/abbs/gmz112. PubMed DOI

Zhuang J., Shen L., Yang L., Huang X., Lu Q., Cui Y., Zheng X., Zhao X., Zhang D., Huang R., et al. TGFbeta1 Promotes Gemcitabine Resistance through Regulating the LncRNA-LET/NF90/miR-145 Signaling Axis in Bladder Cancer. Theranostics. 2017;7:3053–3067. doi: 10.7150/thno.19542. PubMed DOI PMC

Zhang H., Guo Y., Song Y., Shang C. Long Noncoding RNA GAS5 Inhibits Malignant Proliferation and Chemotherapy Resistance to Doxorubicin in Bladder Transitional Cell Carcinoma. Cancer Chemother. Pharmacol. 2017;79:49–55. doi: 10.1007/s00280-016-3194-4. PubMed DOI

Chen X., Xie R., Gu P., Huang M., Han J., Dong W., Xie W., Wang B., He W., Zhong G., et al. Long Noncoding RNA LBCS Inhibits Self-Renewal and Chemoresistance of Bladder Cancer Stem Cells through Epigenetic Silencing of SOX2. Clin. Cancer Res. 2019;25:1389–1403. doi: 10.1158/1078-0432.CCR-18-1656. PubMed DOI

Wang X., Yang B., Ma B. The UCA1/miR-204/Sirt1 Axis Modulates Docetaxel Sensitivity of Prostate Cancer Cells. Cancer Chemother. Pharmacol. 2016;78:1025–1031. doi: 10.1007/s00280-016-3158-8. PubMed DOI

Gao W., Lin S., Cheng C., Zhu A., Hu Y., Shi Z., Zhang X., Hong Z. Long Non-Coding RNA CASC2 Regulates Sprouty2 Via Functioning as a Competing Endogenous RNA for miR-183 to Modulate the Sensitivity of Prostate Cancer Cells to Docetaxel. Arch. Biochem. Biophys. 2019;665:69–78. doi: 10.1016/j.abb.2018.01.013. PubMed DOI

Xue D., Lu H., Xu H.Y., Zhou C.X., He X.Z. Long Noncoding RNA MALAT1 Enhances the Docetaxel Resistance of Prostate Cancer Cells Via miR-145-5p-Mediated Regulation of AKAP12. J. Cell. Mol. Med. 2018;22:3223–3237. doi: 10.1111/jcmm.13604. PubMed DOI PMC

Wang R., Sun Y., Li L., Niu Y., Lin W., Lin C., Antonarakis E.S., Luo J., Yeh S., Chang C. Preclinical Study using Malat1 Small Interfering RNA Or Androgen Receptor Splicing Variant 7 Degradation Enhancer ASC-J9(®) to Suppress Enzalutamide-Resistant Prostate Cancer Progression. Eur. Urol. 2017;72:835–844. doi: 10.1016/j.eururo.2017.04.005. PubMed DOI PMC

Jiang Z., Zhang Y., Chen X., Wu P., Chen D. Long Non-Coding RNA LINC00673 Silencing Inhibits Proliferation and Drug Resistance of Prostate Cancer Cells Via Decreasing KLF4 Promoter Methylation. J. Cell. Mol. Med. 2020;24:1878–1892. doi: 10.1111/jcmm.14883. PubMed DOI PMC

He J., Sun M., Geng H., Tian S. Long Non-Coding RNA Linc00518 Promotes Paclitaxel Resistance of the Human Prostate Cancer by Sequestering miR-216b-5p. Biol. Cell. 2019;111:39–50. doi: 10.1111/boc.201800054. PubMed DOI

Li X., Han X., Wei P., Yang J., Sun J. Knockdown of lncRNA CCAT1 Enhances Sensitivity of Paclitaxel in Prostate Cancer Via Regulating miR-24-3p and FSCN1. Cancer. Biol. Ther. 2020;21:452–462. doi: 10.1080/15384047.2020.1727700. PubMed DOI PMC

Ma Y., Fan B., Ren Z., Liu B., Wang Y. Long Noncoding RNA DANCR Contributes to Docetaxel Resistance in Prostate Cancer through Targeting the miR-34a-5p/JAG1 Pathway. Onco Targets Ther. 2019;12:5485–5497. doi: 10.2147/OTT.S197009. PubMed DOI PMC

Gu P., Chen X., Xie R., Han J., Xie W., Wang B., Dong W., Chen C., Yang M., Jiang J., et al. lncRNA HOXD-AS1 Regulates Proliferation and Chemo-Resistance of Castration-Resistant Prostate Cancer Via Recruiting WDR5. Mol. Ther. J. Am. Soc. Gene Ther. 2017;25:1959–1973. doi: 10.1016/j.ymthe.2017.04.016. PubMed DOI PMC

Wang Z.H., Wang J.H., Wang K.Q., Zhou Y., Wang J. LncRNA FEZF1-AS1 Promoted Chemoresistance, Autophagy and Epithelial-Mesenchymal Transition (EMT) through Regulation of miR-25-3p/ITGB8 Axis in Prostate Cancer. Eur. Rev. Med. Pharmacol. Sci. 2020;24:2281–2293. PubMed

Jiang H., Xiong W., Chen L., Lv Z., Yang C., Li Y. Knockdown of the Long Noncoding RNA HOTTIP Inhibits Cell Proliferation and Enhances Cell Sensitivity to Cisplatin by Suppressing the Wnt/Beta-Catenin Pathway in Prostate Cancer. J. Cell. Biochem. 2019;120:8965–8974. doi: 10.1002/jcb.27851. PubMed DOI

Zhang Z., Zhou N., Huang J., Ho T.T., Zhu Z., Qiu Z., Zhou X., Bai C., Wu F., Xu M., et al. Regulation of Androgen Receptor Splice Variant AR3 by PCGEM1. Oncotarget. 2016;7:15481–15491. doi: 10.18632/oncotarget.7139. PubMed DOI PMC

Zhang A., Zhao J.C., Kim J., Fong K.W., Yang Y.A., Chakravarti D., Mo Y.Y., Yu J. LncRNA HOTAIR Enhances the Androgen-Receptor-Mediated Transcriptional Program and Drives Castration-Resistant Prostate Cancer. Cell. Rep. 2015;13:209–221. doi: 10.1016/j.celrep.2015.08.069. PubMed DOI PMC

Gu P., Chen X., Xie R., Xie W., Huang L., Dong W., Han J., Liu X., Shen J., Huang J., et al. A Novel AR Translational Regulator lncRNA LBCS Inhibits Castration Resistance of Prostate Cancer. Mol. Cancer. 2019;18:1–14. doi: 10.1186/s12943-019-1037-8. PubMed DOI PMC

Wei J., Gan Y., Peng D., Jiang X., Kitazawa R., Xiang Y., Dai Y., Tang Y., Yang J. Long Non-Coding RNA H19 Promotes TDRG1 Expression and Cisplatin Resistance by Sequestering miRNA-106b-5p in Seminoma. Cancer. Med. 2018;7:6247–6257. doi: 10.1002/cam4.1871. PubMed DOI PMC

Znaor A., Lortet-Tieulent J., Laversanne M., Jemal A., Bray F. International Variations and Trends in Renal Cell Carcinoma Incidence and Mortality. Eur. Urol. 2015;67:519–530. doi: 10.1016/j.eururo.2014.10.002. PubMed DOI

Rini B.I., Campbell S.C., Escudier B. Renal Cell Carcinoma. Lancet. 2009;373:1119–1132. doi: 10.1016/S0140-6736(09)60229-4. PubMed DOI

Manini C., López J.I. The Labyrinth of Renal Cell Carcinoma. Cancers. 2020;12:521. doi: 10.3390/cancers12020521. PubMed DOI PMC

Amato R.J. Chemotherapy for Renal Cell Carcinoma. Semin. Oncol. 2000;27:177–186. PubMed

Negrier S., Perol D., Ravaud A., Chevreau C., Bay J.O., Delva R., Sevin E., Caty A., Escudier B., French Immunotherapy Intergroup Medroxyprogesterone, Interferon Alfa-2a, Interleukin 2, Or Combination of both Cytokines in Patients with Metastatic Renal Carcinoma of Intermediate Prognosis: Results of a Randomized Controlled Trial. Cancer. 2007;110:2468–2477. doi: 10.1002/cncr.23056. PubMed DOI

Escudier B., Eisen T., Stadler W.M., Szczylik C., Oudard S., Siebels M., Negrier S., Chevreau C., Solska E., Desai A.A., et al. Sorafenib in Advanced Clear-Cell Renal-Cell Carcinoma. N. Engl. J. Med. 2007;356:125–134. doi: 10.1056/NEJMoa060655. PubMed DOI

Motzer R.J., Hutson T.E., Tomczak P., Michaelson M.D., Bukowski R.M., Oudard S., Negrier S., Szczylik C., Pili R., Bjarnason G.A., et al. Overall Survival and Updated Results for Sunitinib Compared with Interferon Alfa in Patients with Metastatic Renal Cell Carcinoma. J. Clin. Oncol. 2009;27:3584–3590. doi: 10.1200/JCO.2008.20.1293. PubMed DOI PMC

Rini B.I., Plimack E.R., Stus V., Gafanov R., Hawkins R., Nosov D., Pouliot F., Alekseev B., Soulieres D., Melichar B., et al. Pembrolizumab Plus Axitinib Versus Sunitinib for Advanced Renal-Cell Carcinoma. N. Engl. J. Med. 2019;380:1116–1127. doi: 10.1056/NEJMoa1816714. PubMed DOI

Nunes-Xavier C.E., Angulo J.C., Pulido R., López J.I. A Critical Insight into the Clinical Translation of PD-1/PD-L1 Blockade Therapy in Clear Cell Renal Cell Carcinoma. Curr. Urol. Rep. 2019;20:1. doi: 10.1007/s11934-019-0866-8. PubMed DOI

Turajlic S., Xu H., Litchfield K., Rowan A., Horswell S., Chambers T., O’Brien T., Lopez J.I., Watkins T.B.K., Nicol D., et al. Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal. Cell. 2018;173:595–610.e11. doi: 10.1016/j.cell.2018.03.043. PubMed DOI PMC

Turajlic S., Xu H., Litchfield K., Rowan A., Chambers T., Lopez J.I., Nicol D., O’Brien T., Larkin J., Horswell S., et al. Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal. Cell. 2018;173:581–594.e12. doi: 10.1016/j.cell.2018.03.057. PubMed DOI PMC

Seles M., Hutterer G.C., Kiesslich T., Pummer K., Berindan-Neagoe I., Perakis S., Schwarzenbacher D., Stotz M., Gerger A., Pichler M. Current Insights into Long Non-Coding RNAs in Renal Cell Carcinoma. Int. J. Mol. Sci. 2016;17:573. doi: 10.3390/ijms17040573. PubMed DOI PMC

Zhou Y., Zhu Y., Xie Y., Ma X. The Role of Long Non-Coding RNAs in Immunotherapy Resistance. Front. Oncol. 2019;9:1292. doi: 10.3389/fonc.2019.01292. PubMed DOI PMC

Smolle M.A., Prinz F., Calin G.A., Pichler M. Current Concepts of Non-Coding RNA Regulation of Immune Checkpoints in Cancer. Mol. Aspects Med. 2019;70:117–126. doi: 10.1016/j.mam.2019.09.007. PubMed DOI

Li L., Zhu J., Ye F., Duan Z., Zhou J., Huang Z., Wang L. Upregulation of the lncRNA SRLR in Polycystic Ovary Syndrome Regulates Cell Apoptosis and IL-6 Expression. Cell Biochem. Funct. 2020 doi: 10.1002/cbf.3507. PubMed DOI PMC

Xing Q., Li R., Xu A., Qin Z., Tang J., Zhang L., Tang M., Han P., Wang W., Qin C., et al. Genetic Variants in a Long Noncoding RNA Related to Sunitinib Resistance Predict Risk and Survival of Patients with Renal Cell Carcinoma. Cancer Med. 2019;8:2886–2896. doi: 10.1002/cam4.2160. PubMed DOI PMC

Klec C., Prinz F., Pichler M. Involvement of the Long Noncoding RNA NEAT1 in Carcinogenesis. Mol. Oncol. 2019;13:46–60. doi: 10.1002/1878-0261.12404. PubMed DOI PMC

An J., Lv W., Zhang Y. LncRNA NEAT1 Contributes to Paclitaxel Resistance of Ovarian Cancer Cells by Regulating ZEB1 Expression Via miR-194. Onco Targets Ther. 2017;10:5377–5390. doi: 10.2147/OTT.S147586. PubMed DOI PMC

Shin V.Y., Chen J., Cheuk I.W., Siu M.T., Ho C.W., Wang X., Jin H., Kwong A. Long Non-Coding RNA NEAT1 Confers Oncogenic Role in Triple-Negative Breast Cancer through Modulating Chemoresistance and Cancer Stemness. Cell. Death Dis. 2019;10 doi: 10.1038/s41419-019-1513-5. PubMed DOI PMC

Hara T., Makino T., Yamasaki M., Tanaka K., Miyazaki Y., Takahashi T., Kurokawa Y., Nakajima K., Matsuura N., Mori M., et al. Effect of C-Met and CD44v6 Expression in Resistance to Chemotherapy in Esophageal Squamous Cell Carcinoma. Ann. Surg. Oncol. 2019;26:899–906. doi: 10.1245/s10434-018-07126-5. PubMed DOI

Sun Z.Y., Jian Y.K., Zhu H.Y., Li B. lncRNAPVT1 Targets miR-152 to Enhance Chemoresistance of Osteosarcoma to Gemcitabine through Activating C-MET/PI3K/AKT Pathway. Pathol. Res. Pract. 2019;215:555–563. doi: 10.1016/j.prp.2018.12.013. PubMed DOI

Pu Y., Zhao F., Li Y., Cui M., Wang H., Meng X., Cai S. The miR-34a-5p Promotes the Multi-Chemoresistance of Osteosarcoma Via Repression of the AGTR1 Gene. BMC Cancer. 2017;17:45. doi: 10.1186/s12885-016-3002-x. PubMed DOI PMC

Yan Y., Xu Z., Chen X., Wang X., Zeng S., Zhao Z., Qian L., Li Z., Wei J., Huo L., et al. Novel Function of lncRNA ADAMTS9-AS2 in Promoting Temozolomide Resistance in Glioblastoma Via Upregulating the FUS/MDM2 Ubiquitination Axis. Front. Cell. Dev. Biol. 2019;7:217. doi: 10.3389/fcell.2019.00217. PubMed DOI PMC

Shi Y.F., Lu H., Wang H.B. Downregulated lncRNA ADAMTS9-AS2 in Breast Cancer Enhances Tamoxifen Resistance by Activating microRNA-130a-5p. Eur. Rev. Med. Pharmacol. Sci. 2019;23:1563–1573. PubMed

Ma C., Shi X., Zhu Q., Li Q., Liu Y., Yao Y., Song Y. The Growth Arrest-Specific Transcript 5 (GAS5): A Pivotal Tumor Suppressor Long Noncoding RNA in Human Cancers. Tumour Biol. 2016;37:1437–1444. doi: 10.1007/s13277-015-4521-9. PubMed DOI

Gao Z.Q., Wang J.F., Chen D.H., Ma X.S., Yang W., Zhe T., Dang X.W. Long Non-Coding RNA GAS5 Antagonizes the Chemoresistance of Pancreatic Cancer Cells through Down-Regulation of miR-181c-5p. Biomed. Pharmacother. 2018;97:809–817. doi: 10.1016/j.biopha.2017.10.157. PubMed DOI

Chen Z., Pan T., Jiang D., Jin L., Geng Y., Feng X., Shen A., Zhang L. The lncRNA-GAS5/miR-221-3p/DKK2 Axis Modulates ABCB1-Mediated Adriamycin Resistance of Breast Cancer Via the Wnt/Beta-Catenin Signaling Pathway. Mol. Ther. Nucleic Acids. 2020;19:1434–1448. doi: 10.1016/j.omtn.2020.01.030. PubMed DOI PMC

Chen D., Wang R., Yu C., Cao F., Zhang X., Yan F., Chen L., Zhu H., Yu Z., Feng J. FOX-A1 Contributes to Acquisition of Chemoresistance in Human Lung Adenocarcinoma Via Transactivation of SOX5. Ebiomedicine. 2019;44:150–161. doi: 10.1016/j.ebiom.2019.05.046. PubMed DOI PMC

Dai X., Fang M., Li S., Yan Y., Zhong Y., Du B. miR-21 is Involved in Transforming Growth Factor Beta1-Induced Chemoresistance and Invasion by Targeting PTEN in Breast Cancer. Oncol. Lett. 2017;14:6929–6936. PubMed PMC

Richters A., Aben K.K.H., Kiemeney L.A.L.M. The Global Burden of Urinary Bladder Cancer: An Update. World J. Urol. 2019;38:1895–1904. doi: 10.1007/s00345-019-02984-4. PubMed DOI PMC

Mitra A.P., Lin H., Datar R.H., Cote R.J. Molecular Biology of Bladder Cancer: Prognostic and Clinical Implications. Clin. Genitourin. Cancer. 2006;5:67–77. PubMed

Knowles M.A., Hurst C.D. Molecular Biology of Bladder Cancer: New Insights into Pathogenesis and Clinical Diversity. Nat. Rev. Cancer. 2015;15:25–41. doi: 10.1038/nrc3817. PubMed DOI

Sexton W.J., Wiegand L.R., Correa J.J., Politis C., Dickinson S.I., Kang L.C. Bladder Cancer: A Review of Non-Muscle Invasive Disease. Cancer Control. 2010;17:256–268. doi: 10.1177/107327481001700406. PubMed DOI

Babjuk M., Burger M., Zigeuner R., Shariat S.F., van Rhijn B.W., Compérat E., Sylvester R.J., Kaasinen E., Böhle A., Palou Redorta J., et al. EAU Guidelines on Non-Muscle-Invasive Urothelial Carcinoma of the Bladder: Update 2013. Eur. Urol. 2013;64:639–653. doi: 10.1016/j.eururo.2013.06.003. PubMed DOI

Alfred Witjes J., Lebret T., Compérat E.M., Cowan N.C., De Santis M., Bruins H.M., Hernández V., Espinós E.L., Dunn J., Rouanne M., et al. Updated 2016 EAU Guidelines on Muscle-Invasive and Metastatic Bladder Cancer. Eur. Urol. 2017;71:462–475. doi: 10.1016/j.eururo.2016.06.020. PubMed DOI

Loriot Y., Necchi A., Park S.H., Garcia-Donas J., Huddart R., Burgess E., Fleming M., Rezazadeh A., Mellado B., Varlamov S., et al. Erdafitinib in Locally Advanced Or Metastatic Urothelial Carcinoma. N. Engl. J. Med. 2019;381:338–348. doi: 10.1056/NEJMoa1817323. PubMed DOI

Han Y., Liu Y., Gui Y., Cai Z. Long Intergenic Non-Coding RNA TUG1 is Overexpressed in Urothelial Carcinoma of the Bladder. J. Surg. Oncol. 2013;107:555–559. doi: 10.1002/jso.23264. PubMed DOI

Lebrun L., Milowich D., Le Mercier M., Allard J., Van Eycke Y.R., Roumeguere T., Decaestecker C., Salmon I., Rorive S. UCA1 Overexpression is Associated with Less Aggressive Subtypes of Bladder Cancer. Oncol. Rep. 2018;40:2497–2506. doi: 10.3892/or.2018.6697. PubMed DOI PMC

Kukcinaviciute E., Jonusiene V., Sasnauskiene A., Dabkeviciene D., Eidenaite E., Laurinavicius A. Significance of Notch and Wnt Signaling for Chemoresistance of Colorectal Cancer Cells HCT116. J. Cell. Biochem. 2018;119:5913–5920. doi: 10.1002/jcb.26783. PubMed DOI

Li J.H., Luo N., Zhong M.Z., Xiao Z.Q., Wang J.X., Yao X.Y., Peng Y., Cao J. Inhibition of microRNA-196a might Reverse Cisplatin Resistance of A549/DDP Non-Small-Cell Lung Cancer Cell Line. Tumour Biol. 2016;37:2387–2394. doi: 10.1007/s13277-015-4017-7. PubMed DOI

Liu Y., Zhou D., Li G., Ming X., Tu Y., Tian J., Lu H., Yu B. Long Non Coding RNA-UCA1 Contributes to Cardiomyocyte Apoptosis by Suppression of p27 Expression. Cell. Physiol. Biochem. 2015;35:1986–1998. doi: 10.1159/000374006. PubMed DOI

Geng J., Klionsky D.J. The Atg8 and Atg12 Ubiquitin-Like Conjugation Systems in Macroautophagy. ‘Protein Modifications: Beyond the Usual Suspects’ Review Series. EMBO Rep. 2008;9:859–864. doi: 10.1038/embor.2008.163. PubMed DOI PMC

Sui X., Chen R., Wang Z., Huang Z., Kong N., Zhang M., Han W., Lou F., Yang J., Zhang Q., et al. Autophagy and Chemotherapy Resistance: A Promising Therapeutic Target for Cancer Treatment. Cell. Death Dis. 2013;4:e838. doi: 10.1038/cddis.2013.350. PubMed DOI PMC

Young T.L., Matsuda T., Cepko C.L. The Noncoding RNA Taurine Upregulated Gene 1 is Required for Differentiation of the Murine Retina. Curr. Biol. 2005;15:501–512. doi: 10.1016/j.cub.2005.02.027. PubMed DOI

Sun J., Ding C., Yang Z., Liu T., Zhang X., Zhao C., Wang J. The Long Non-Coding RNA TUG1 Indicates a Poor Prognosis for Colorectal Cancer and Promotes Metastasis by Affecting Epithelial-Mesenchymal Transition. J. Transl. Med. 2016;14:42. doi: 10.1186/s12967-016-0786-z. PubMed DOI PMC

Zhang E., He X., Yin D., Han L., Qiu M., Xu T., Xia R., Xu L., Yin R., De W. Increased Expression of Long Noncoding RNA TUG1 Predicts a Poor Prognosis of Gastric Cancer and Regulates Cell Proliferation by Epigenetically Silencing of p57. Cell. Death Dis. 2016;7:e2109. doi: 10.1038/cddis.2015.356. PubMed DOI PMC

Zhang E.B., Yin D.D., Sun M., Kong R., Liu X.H., You L.H., Han L., Xia R., Wang K.M., Yang J.S., et al. P53-Regulated Long Non-Coding RNA TUG1 Affects Cell Proliferation in Human Non-Small Cell Lung Cancer, Partly through Epigenetically Regulating HOXB7 Expression. Cell. Death Dis. 2014;5:e1243. doi: 10.1038/cddis.2014.201. PubMed DOI PMC

Huang M.D., Chen W.M., Qi F.Z., Sun M., Xu T.P., Ma P., Shu Y.Q. Long Non-Coding RNA TUG1 is Up-Regulated in Hepatocellular Carcinoma and Promotes Cell Growth and Apoptosis by Epigenetically Silencing of KLF2. Mol. Cancer. 2015;14:165. doi: 10.1186/s12943-015-0431-0. PubMed DOI PMC

Iliev R., Kleinova R., Juracek J., Dolezel J., Ozanova Z., Fedorko M., Pacik D., Svoboda M., Stanik M., Slaby O. Overexpression of Long Non-Coding RNA TUG1 Predicts Poor Prognosis and Promotes Cancer Cell Proliferation and Migration in High-Grade Muscle-Invasive Bladder Cancer. Tumour Biol. 2016;37:13385–13390. doi: 10.1007/s13277-016-5177-9. PubMed DOI

Shen C.J., Cheng Y.M., Wang C.L. LncRNA PVT1 Epigenetically Silences miR-195 and Modulates EMT and Chemoresistance in Cervical Cancer Cells. J. Drug Target. 2017;25:637–644. doi: 10.1080/1061186X.2017.1307379. PubMed DOI

Zhang X.W., Bu P., Liu L., Zhang X.Z., Li J. Overexpression of Long Non-Coding RNA PVT1 in Gastric Cancer Cells Promotes the Development of Multidrug Resistance. Biochem. Biophys. Res. Commun. 2015;462:227–232. doi: 10.1016/j.bbrc.2015.04.121. PubMed DOI

Chen L., Han X., Hu Z., Chen L. The PVT1/miR-216b/Beclin-1 Regulates Cisplatin Sensitivity of NSCLC Cells Via Modulating Autophagy and Apoptosis. Cancer Chemother. Pharmacol. 2019;83:921–931. doi: 10.1007/s00280-019-03808-3. PubMed DOI

Su F., He W., Chen C., Liu M., Liu H., Xue F., Bi J., Xu D., Zhao Y., Huang J., et al. The Long Non-Coding RNA FOXD2-AS1 Promotes Bladder Cancer Progression and Recurrence through a Positive Feedback Loop with Akt and E2F1. Cell. Death Dis. 2018;9:233–239. doi: 10.1038/s41419-018-0275-9. PubMed DOI PMC

Liu X., Yao D., Liu C., Cao Y., Yang Q., Sun Z., Liu D. Overexpression of ABCC3 Promotes Cell Proliferation, Drug Resistance, and Aerobic Glycolysis and is Associated with Poor Prognosis in Urinary Bladder Cancer Patients. Tumour Biol. 2016;37:8367–8374. doi: 10.1007/s13277-015-4703-5. PubMed DOI

Bullrich F., Fujii H., Calin G., Mabuchi H., Negrini M., Pekarsky Y., Rassenti L., Alder H., Reed J.C., Keating M.J., et al. Characterization of the 13q14 Tumor Suppressor Locus in CLL: Identification of ALT1, an Alternative Splice Variant of the LEU2 Gene. Cancer Res. 2001;61:6640–6648. PubMed

Calin G.A., Croce C.M. Chronic Lymphocytic Leukemia: Interplay between Noncoding RNAs and Protein-Coding Genes. Blood. 2009;114:4761–4770. doi: 10.1182/blood-2009-07-192740. PubMed DOI PMC

Liu Y., Corcoran M., Rasool O., Ivanova G., Ibbotson R., Grandér D., Iyengar A., Baranova A., Kashuba V., Merup M., et al. Cloning of Two Candidate Tumor Suppressor Genes within a 10 Kb Region on Chromosome 13q14, Frequently Deleted in Chronic Lymphocytic Leukemia. Oncogene. 1997;15:2463–2473. doi: 10.1038/sj.onc.1201643. PubMed DOI

Calin G.A., Dumitru C.D., Shimizu M., Bichi R., Zupo S., Noch E., Aldler H., Rattan S., Keating M., Rai K., et al. Frequent Deletions and Down-Regulation of Micro- RNA Genes miR15 and miR16 at 13q14 in Chronic Lymphocytic Leukemia. Proc. Natl. Acad. Sci. USA. 2002;99:15524–15529. doi: 10.1073/pnas.242606799. PubMed DOI PMC

Ciccone M., Calin G.A. MicroRNAs in Chronic Lymphocytic Leukemia: An Old Disease with New Genetic Insights. Microrna. 2016;5:106–112. doi: 10.2174/2211536605666160825150219. PubMed DOI

Van Roosbroeck K., Calin G.A. MicroRNAs in Chronic Lymphocytic Leukemia: Miracle or miRage for Prognosis and Targeted Therapies? Semin. Oncol. 2016;43:209–214. doi: 10.1053/j.seminoncol.2016.02.015. PubMed DOI PMC

Van Roosbroeck K., Bayraktar R., Calin S., Bloehdorn J., Dragomir M.P., Okubo K., Bertilaccio M.T.S., Zupo S., You M.J., Gaidano G., et al. The Involvement of microRNA in the Pathogenesis of Richter Syndrome. Haematologica. 2019;104:1004–1015. doi: 10.3324/haematol.2018.203828. PubMed DOI PMC

Lee S., Luo W., Shah T., Yin C., O’Connell T., Chung T.H., Perkins S.L., Miles R.R., Ayello J., Morris E., et al. The Effects of DLEU1 Gene Expression in Burkitt Lymphoma (BL): Potential Mechanism of Chemoimmunotherapy Resistance in BL. Oncotarget. 2017;8:27839–27853. doi: 10.18632/oncotarget.15711. PubMed DOI PMC

Liu C., Tian X., Zhang J., Jiang L. Long Non-Coding RNA DLEU1 Promotes Proliferation and Invasion by Interacting with miR-381 and Enhancing HOXA13 Expression in Cervical Cancer. Front. Genet. 2018;9:629. doi: 10.3389/fgene.2018.00629. PubMed DOI PMC

Liu T., Han Z., Li H., Zhu Y., Sun Z., Zhu A. LncRNA DLEU1 Contributes to Colorectal Cancer Progression Via Activation of KPNA3. Mol. Cancer. 2018;17:118. doi: 10.1186/s12943-018-0873-2. PubMed DOI PMC

Zhang S., Guan Y., Liu X., Ju M., Zhang Q. Long Non-Coding RNA DLEU1 Exerts an Oncogenic Function in Non-Small Cell Lung Cancer. Biomed. Pharmacother. 2019;109:985–990. doi: 10.1016/j.biopha.2018.10.175. PubMed DOI

Li W., Chang J., Wang S., Liu X., Peng J., Huang D., Sun M., Chen Z., Zhang W., Guo W., et al. miRNA-99b-5p Suppresses Liver Metastasis of Colorectal Cancer by Down-Regulating mTOR. Oncotarget. 2015;6:24448–24462. doi: 10.18632/oncotarget.4423. PubMed DOI PMC

Kang J., Lee S.Y., Lee S.Y., Kim Y.J., Park J.Y., Kwon S.J., Na M.J., Lee E.J., Jeon H.S., Son J.W. microRNA-99b Acts as a Tumor Suppressor in Non-Small Cell Lung Cancer by Directly Targeting Fibroblast Growth Factor Receptor 3. Exp. Ther. Med. 2012;3:149–153. doi: 10.3892/etm.2011.366. PubMed DOI PMC

Van Rhijn B.W., Lurkin I., Radvanyi F., Kirkels W.J., van der Kwast T.H., Zwarthoff E.C. The Fibroblast Growth Factor Receptor 3 (FGFR3) Mutation is a Strong Indicator of Superficial Bladder Cancer with Low Recurrence Rate. Cancer Res. 2001;61:1265–1268. PubMed

Song K., Li Q., Jiang Z.Z., Guo C.W., Li P. Heparan Sulfate D-Glucosaminyl 3-O-Sulfotransferase-3B1, a Novel Epithelial-Mesenchymal Transition Inducer in Pancreatic Cancer. Cancer. Biol. Ther. 2011;12:388–398. doi: 10.4161/cbt.12.5.15957. PubMed DOI

Chen S., Jiao J.W., Sun K.X., Zong Z.H., Zhao Y. MicroRNA-133b Targets Glutathione S-Transferase Ï€ Expression to Increase Ovarian Cancer Cell Sensitivity to Chemotherapy Drugs. Drug Des. Dev. Ther. 2015;9:5225–5235. PubMed PMC

Lv L., Li Q., Chen S., Zhang X., Tao X., Tang X., Wang S., Che G., Yu Y., He L. miR-133b Suppresses Colorectal Cancer Cell Stemness and Chemoresistance by Targeting Methyltransferase DOT1L. Exp. Cell Res. 2019;385:111597. doi: 10.1016/j.yexcr.2019.111597. PubMed DOI

Zou Y., Yang J., Wu J., Luo C., Huang Y. miR-133b Induces Chemoresistance of Osteosarcoma Cells to Cisplatin Treatment by Promoting Cell Death, Migration and Invasion. Oncol. Lett. 2018;15:1097–1102. doi: 10.3892/ol.2017.7432. PubMed DOI PMC

Vaziri H., Dessain S.K., Ng Eaton E., Imai S.I., Frye R.A., Pandita T.K., Guarente L., Weinberg R.A. hSIR2(SIRT1) Functions as an NAD-Dependent p53 Deacetylase. Cell. 2001;107:149–159. doi: 10.1016/S0092-8674(01)00527-X. PubMed DOI

Bertozzi D., Iurlaro R., Sordet O., Marinello J., Zaffaroni N., Capranico G. Characterization of Novel Antisense HIF-1alpha Transcripts in Human Cancers. Cell. Cycle. 2011;10:3189–3197. doi: 10.4161/cc.10.18.17183. PubMed DOI

Chen M., Zhuang C., Liu Y., Li J., Dai F., Xia M., Zhan Y., Lin J., Chen Z., He A., et al. Tetracycline-Inducible shRNA Targeting Antisense Long Non-Coding RNA HIF1A-AS2 Represses the Malignant Phenotypes of Bladder Cancer. Cancer Lett. 2016;376:155–164. doi: 10.1016/j.canlet.2016.03.037. PubMed DOI

Mineo M., Ricklefs F., Rooj A.K., Lyons S.M., Ivanov P., Ansari K.I., Nakano I., Chiocca E.A., Godlewski J., Bronisz A. The Long Non-Coding RNA HIF1A-AS2 Facilitates the Maintenance of Mesenchymal Glioblastoma Stem-Like Cells in Hypoxic Niches. Cell Rep. 2016;15:2500–2509. doi: 10.1016/j.celrep.2016.05.018. PubMed DOI PMC

Li L.J., Zhu J.L., Bao W.S., Chen D.K., Huang W.W., Weng Z.L. Long Noncoding RNA GHET1 Promotes the Development of Bladder Cancer. Int. J. Clin. Exp. Pathol. 2014;7:7196–7205. PubMed PMC

Li X., Wang H., Wang J., Chen Y., Yin X., Shi G., Li H., Hu Z., Liang X. Emodin Enhances Cisplatin-Induced Cytotoxicity in Human Bladder Cancer Cells through ROS Elevation and MRP1 Downregulation. BMC Cancer. 2016;16:578. doi: 10.1186/s12885-016-2640-3. PubMed DOI PMC

Cao W., Liu B., Ma H. Long Non-Coding RNA GHET1 Promotes Viability, Migration and Invasion of Glioma Cell Line U251 by Down-Regulation of miR-216a. Eur. Rev. Med. Pharmacol. Sci. 2019;23:1591–1599. PubMed

Hu Z., Lin Y., Chen H., Mao Y., Wu J., Zhu Y., Xu X., Xu X., Li S., Zheng X., et al. MicroRNA-101 Suppresses Motility of Bladder Cancer Cells by Targeting C-Met. Biochem. Biophys. Res. Commun. 2013;435:82–87. doi: 10.1016/j.bbrc.2013.04.042. PubMed DOI

Zhu H., Yun F., Shi X., Wang D. VEGF-C Inhibition Reverses Resistance of Bladder Cancer Cells to Cisplatin Via Upregulating Maspin. Mol. Med. Rep. 2015;12:3163–3169. doi: 10.3892/mmr.2015.3684. PubMed DOI

Li B., Xie D., Zhang H. MicroRNA-101-3p Advances Cisplatin Sensitivity in Bladder Urothelial Carcinoma through Targeted Silencing EZH2. J. Cancer. 2019;10:2628–2634. doi: 10.7150/jca.33117. PubMed DOI PMC

Zhang W., Xiong Z., Wei T., Li Q., Tan Y., Ling L., Feng X. Nuclear Factor 90 Promotes Angiogenesis by Regulating HIF-1α/VEGF-A Expression through the PI3K/Akt Signaling Pathway in Human Cervical Cancer. Cell. Death Dis. 2018;9:276. doi: 10.1038/s41419-018-0334-2. PubMed DOI PMC

Sakamoto S., Aoki K., Higuchi T., Todaka H., Morisawa K., Tamaki N., Hatano E., Fukushima A., Taniguchi T., Agata Y. The NF90-NF45 Complex Functions as a Negative Regulator in the microRNA Processing Pathway. Mol. Cell. Biol. 2009;29:3754–3769. doi: 10.1128/MCB.01836-08. PubMed DOI PMC

Davis-Dusenbery B., Chan M.C., Reno K.E., Weisman A.S., Layne M.D., Lagna G., Hata A. Down-Regulation of Kruppel-Like Factor-4 (KLF4) by microRNA-143/145 is Critical for Modulation of Vascular Smooth Muscle Cell Phenotype by Transforming Growth Factor-Beta and Bone Morphogenetic Protein 4. J. Biol. Chem. 2011;286:28097–28110. doi: 10.1074/jbc.M111.236950. PubMed DOI PMC

Wang Y., Song Q., Huang X., Chen Z., Zhang F., Wang K., Huang G., Shen H. Long Noncoding RNA GAS5 Promotes Apoptosis in Primary Nucleus Pulposus Cells Derived from the Human Intervertebral Disc Via Bcl‑2 Downregulation and Caspase‑3 Upregulation. Mol. Med. Rep. 2019;19:2164–2172. PubMed PMC

Chen X., Gu P., Xie R., Han J., Liu H., Wang B., Xie W., Xie W., Zhong G., Chen C., et al. Heterogeneous Nuclear Ribonucleoprotein K is Associated with Poor Prognosis and Regulates Proliferation and Apoptosis in Bladder Cancer. J. Cell. Mol. Med. 2017;21:1266–1279. doi: 10.1111/jcmm.12999. PubMed DOI PMC

Juan A.H., Derfoul A., Feng X., Ryall J.G., Dell’Orso S., Pasut A., Zare H., Simone J.M., Rudnicki M.A., Sartorelli V. Polycomb EZH2 Controls Self-Renewal and Safeguards the Transcriptional Identity of Skeletal Muscle Stem Cells. Genes Dev. 2011;25:789–794. doi: 10.1101/gad.2027911. PubMed DOI PMC

Zhu F., Qian W., Zhang H., Liang Y., Wu M., Zhang Y., Zhang X., Gao Q., Li Y. SOX2 is a Marker for Stem-Like Tumor Cells in Bladder Cancer. Stem Cell Rep. 2017;9:429–437. doi: 10.1016/j.stemcr.2017.07.004. PubMed DOI PMC

Siegel R.L., Miller K.D., Jemal A. Cancer Statistics, 2019. CA Cancer. J. Clin. 2019;69:7–34. PubMed

Mosillo C., Iacovelli R., Ciccarese C., Fantinel E., Bimbatti D., Brunelli M., Bisogno I., Kinspergher S., Buttigliero C., Tucci M., et al. De Novo Metastatic Castration Sensitive Prostate Cancer: State of Art and Future Perspectives. Cancer Treat. Rev. 2018;70:67–74. doi: 10.1016/j.ctrv.2018.08.005. PubMed DOI

Pagliarulo V., Bracarda S., Eisenberger M.A., Mottet N., Schroder F.H., Sternberg C.N., Studer U.E. Contemporary Role of Androgen Deprivation Therapy for Prostate Cancer. Eur. Urol. 2012;61:11–25. doi: 10.1016/j.eururo.2011.08.026. PubMed DOI PMC

Mansinho A., Macedo D., Fernandes I., Costa L. Castration-Resistant Prostate Cancer: Mechanisms, Targets and Treatment. Adv. Exp. Med. Biol. 2018;1096:117–133. PubMed

Ryan C.J., Smith M.R., de Bono J.S., Molina A., Logothetis C.J., de Souza P., Fizazi K., Mainwaring P., Piulats J.M., Ng S., et al. Abiraterone in Metastatic Prostate Cancer without Previous Chemotherapy. N. Engl. J. Med. 2013;368:138–148. doi: 10.1056/NEJMoa1209096. PubMed DOI PMC

Petrylak D.P., Tangen C.M., Hussain M.H., Lara P.N., Jr., Jones J.A., Taplin M.E., Burch P.A., Berry D., Moinpour C., Kohli M., et al. Docetaxel and Estramustine Compared with Mitoxantrone and Prednisone for Advanced Refractory Prostate Cancer. N. Engl. J. Med. 2004;351:1513–1520. doi: 10.1056/NEJMoa041318. PubMed DOI

De Wit R., de Bono J., Sternberg C.N., Fizazi K., Tombal B., Wulfing C., Kramer G., Eymard J.C., Bamias A., Carles J., et al. Cabazitaxel Versus Abiraterone Or Enzalutamide in Metastatic Prostate Cancer. N. Engl. J. Med. 2019;381:2506–2518. doi: 10.1056/NEJMoa1911206. PubMed DOI

Fabris L., Ceder Y., Chinnaiyan A.M., Jenster G.W., Sorensen K.D., Tomlins S., Visakorpi T., Calin G.A. The Potential of MicroRNAs as Prostate Cancer Biomarkers. Eur. Urol. 2016;70:312–322. doi: 10.1016/j.eururo.2015.12.054. PubMed DOI PMC

Salameh A., Lee A.K., CardÃ3-Vila M., Nunes D.N., Efstathiou E., Staquicini F.I., Dobroff A.S., MarchiÃ2 S., Navone N.M., Hosoya H., et al. PRUNE2 is a Human Prostate Cancer Suppressor Regulated by the Intronic Long Noncoding RNA PCA3. Proc. Natl. Acad. Sci. USA. 2015;112:8403–8408. doi: 10.1073/pnas.1507882112. PubMed DOI PMC

Wang H., Guan Z., He K., Qian J., Cao J., Teng L. LncRNA UCA1 in Anti-Cancer Drug Resistance. Oncotarget. 2017;8:64638–64650. doi: 10.18632/oncotarget.18344. PubMed DOI PMC

He C., Lu X., Yang F., Qin L., Guo Z., Sun Y., Wu J. LncRNA UCA1 Acts as a Sponge of miR-204 to Up-Regulate CXCR4 Expression and Promote Prostate Cancer Progression. Biosci. Rep. 2019;39 doi: 10.1042/BSR20181465. PubMed DOI PMC

Yu Y., Gao F., He Q., Li G., Ding G. lncRNA UCA1 Functions as a ceRNA to Promote Prostate Cancer Progression Via Sponging miR143. Mol. Ther. Nucleic Acids. 2020;19:751–758. doi: 10.1016/j.omtn.2019.11.021. PubMed DOI PMC

Kojima K., Ohhashi R., Fujita Y., Hamada N., Akao Y., Nozawa Y., Deguchi T., Ito M. A Role for SIRT1 in Cell Growth and Chemoresistance in Prostate Cancer PC3 and DU145 Cells. Biochem. Biophys. Res. Commun. 2008;373:423–428. doi: 10.1016/j.bbrc.2008.06.045. PubMed DOI

Robey R.W., Pluchino K.M., Hall M.D., Fojo A.T., Bates S.E., Gottesman M.M. Revisiting the Role of ABC Transporters in Multidrug-Resistant Cancer. Nat. Rev. Cancer. 2018;18:452–464. doi: 10.1038/s41568-018-0005-8. PubMed DOI PMC

Lee N.K., Lee J.H., Ivan C., Ling H., Zhang X., Park C.H., Calin G.A., Lee S.K. MALAT1 Promoted Invasiveness of Gastric Adenocarcinoma. BMC Cancer. 2017;17:46. doi: 10.1186/s12885-016-2988-4. PubMed DOI PMC

Smolle M.A., Bauernhofer T., Pummer K., Calin G.A., Pichler M. Current Insights into Long Non-Coding RNAs (LncRNAs) in Prostate Cancer. Int. J. Mol. Sci. 2017;18:473. doi: 10.3390/ijms18020473. PubMed DOI PMC

Hao T., Wang Z., Yang J., Zhang Y., Shang Y., Sun J. MALAT1 Knockdown Inhibits Prostate Cancer Progression by Regulating miR-140/BIRC6 Axis. Biomed. Pharmacother. 2020;123:109666. doi: 10.1016/j.biopha.2019.109666. PubMed DOI

Wang D., Ding L., Wang L., Zhao Y., Sun Z., Karnes R.J., Zhang J., Huang H. LncRNA MALAT1 Enhances Oncogenic Activities of EZH2 in Castration-Resistant Prostate Cancer. Oncotarget. 2015;6:41045–41055. doi: 10.18632/oncotarget.5728. PubMed DOI PMC

Dai X., Liang Z., Liu L., Guo K., Xu S., Wang H. Silencing of MALAT1 Inhibits Migration and Invasion by Sponging miR13p in Prostate Cancer Cells. Mol. Med. Rep. 2019;20:3499–3508. PubMed PMC

Hussain M., Fizazi K., Saad F., Rathenborg P., Shore N., Ferreira U., Ivashchenko P., Demirhan E., Modelska K., Phung D., et al. Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer. N. Engl. J. Med. 2018;378:2465–2474. doi: 10.1056/NEJMoa1800536. PubMed DOI PMC

Antonarakis E.S., Lu C., Wang H., Luber B., Nakazawa M., Roeser J.C., Chen Y., Mohammad T.A., Chen Y., Fedor H.L., et al. AR-V7 and Resistance to Enzalutamide and Abiraterone in Prostate Cancer. N. Engl. J. Med. 2014;371:1028–1038. doi: 10.1056/NEJMoa1315815. PubMed DOI PMC

Ghaleb A.M., Yang V.W. Kruppel-Like Factor 4 (KLF4): What we Currently Know. Gene. 2017;611:27–37. doi: 10.1016/j.gene.2017.02.025. PubMed DOI PMC

Ba M.C., Long H., Cui S.Z., Gong Y.F., Yan Z.F., Wu Y.B., Tu Y.N. Long Noncoding RNA LINC00673 Epigenetically Suppresses KLF4 by Interacting with EZH2 and DNMT1 in Gastric Cancer. Oncotarget. 2017;8:95542–95553. doi: 10.18632/oncotarget.20980. PubMed DOI PMC

Sun Z., Yan B. Multiple Roles and Regulatory Mechanisms of the Transcription Factor GATA6 in Human Cancers. Clin. Genet. 2020;97:64–72. doi: 10.1111/cge.13630. PubMed DOI

Luo M., Wu L., Zhang K., Wang H., Wu S., O’Connell D., Gao T., Zhong H., Yang Y. miR-216b Enhances the Efficacy of Vemurafenib by Targeting Beclin-1, UVRAG and ATG5 in Melanoma. Cell Signal. 2018;42:30–43. doi: 10.1016/j.cellsig.2017.09.024. PubMed DOI

Ghafouri-Fard S., Taheri M. Colon Cancer-Associated Transcripts 1 and 2: Roles and Functions in Human Cancers. J. Cell. Physiol. 2019;234:14581–14600. doi: 10.1002/jcp.28176. PubMed DOI

Ozawa T., Matsuyama T., Toiyama Y., Takahashi N., Ishikawa T., Uetake H., Yamada Y., Kusunoki M., Calin G., Goel A. CCAT1 and CCAT2 Long Noncoding RNAs, Located within the 8q.24.21 ‘Gene Desert’, Serve as Important Prognostic Biomarkers in Colorectal Cancer. Ann. Oncol. 2017;28:1882–1888. doi: 10.1093/annonc/mdx248. PubMed DOI PMC

Chen H., He Y., Hou Y.S., Chen D.Q., He S.L., Cao Y.F., Wu X.M. Long Non-Coding RNA CCAT1 Promotes the Migration and Invasion of Prostate Cancer PC-3 Cells. Eur. Rev. Med. Pharmacol. Sci. 2018;22:2991–2996. PubMed

You Z., Liu C., Wang C., Ling Z., Wang Y., Wang Y., Zhang M., Chen S., Xu B., Guan H., et al. LncRNA CCAT1 Promotes Prostate Cancer Cell Proliferation by Interacting with DDX5 and MIR-28-5P. Mol. Cancer. Ther. 2019;18:2469–2479. doi: 10.1158/1535-7163.MCT-19-0095. PubMed DOI

Barros-Silva D., Lobo J., Guimaraes-Teixeira C., Carneiro I., Oliveira J., Martens-Uzunova E.S., Henrique R., Jeronimo C. VIRMA-Dependent N6-Methyladenosine Modifications Regulate the Expression of Long Non-Coding RNAs CCAT1 and CCAT2 in Prostate Cancer. Cancers. 2020;12:771. doi: 10.3390/cancers12040771. PubMed DOI PMC

Pan Y., Chen J., Tao L., Zhang K., Wang R., Chu X., Chen L. Long Noncoding RNA ROR Regulates Chemoresistance in Docetaxel-Resistant Lung Adenocarcinoma Cells Via Epithelial Mesenchymal Transition Pathway. Oncotarget. 2017;8:33144–33158. doi: 10.18632/oncotarget.16562. PubMed DOI PMC

Zhang Y., Lu Y., Zhang C., Huang D., Wu W., Zhang Y., Shen J., Cai Y., Chen W., Yao W. FSCN1 Increases Doxorubicin Resistance in Hepatocellular Carcinoma through Promotion of Epithelial-Mesenchymal Transition. Int. J. Oncol. 2018;52:1455–1464. PubMed PMC

Grochowski C.M., Loomes K.M., Spinner N.B. Jagged1 (JAG1): Structure, Expression, and Disease Associations. Gene. 2016;576:381–384. doi: 10.1016/j.gene.2015.10.065. PubMed DOI PMC

Kim T.M., Ha S.A., Kim H.K., Yoo J., Kim S., Yim S.H., Jung S.H., Kim D.W., Chung Y.J., Kim J.W. Gene Expression Signatures Associated with the In Vitro Resistance to Two Tyrosine Kinase Inhibitors, Nilotinib and Imatinib. Blood Cancer J. 2011;1:e32. doi: 10.1038/bcj.2011.32. PubMed DOI PMC

Naghizadeh S., Mohammadi A., Duijf P.H.G., Baradaran B., Safarzadeh E., Cho W.C., Mansoori B. The Role of miR-34 in Cancer Drug Resistance. J. Cell. Physiol. 2020 doi: 10.1002/jcp.29640. PubMed DOI

Li L., Wang Y., Zhang X., Huang Q., Diao Y., Yin H., Liu H. Long Non-Coding RNA HOXD-AS1 in Cancer. Clin. Chim. Acta. 2018;487:197–201. doi: 10.1016/j.cca.2018.10.002. PubMed DOI

Kim J., Banerjee T., Vinckevicius A., Luo Q., Parker J.B., Baker M.R., Radhakrishnan I., Wei J., Barish G.D., Chakravarti D. A Role for WDR5 in Integrating Threonine 11 Phosphorylation to Lysine 4 Methylation on Histone H3 during Androgen Signaling and in Prostate Cancer. Mol. Cell. 2014;54:613–625. doi: 10.1016/j.molcel.2014.03.043. PubMed DOI PMC

Zhou Y., Xu S., Xia H., Gao Z., Huang R., Tang E., Jiang X. Long Noncoding RNA FEZF1-AS1 in Human Cancers. Clin. Chim. Acta. 2019;497:20–26. doi: 10.1016/j.cca.2019.07.004. PubMed DOI

Cui Y., Wu F., Tian D., Wang T., Lu T., Huang X., Zhang P., Qin L. miR-199a-3p Enhances Cisplatin Sensitivity of Ovarian Cancer Cells by Targeting ITGB8. Oncol. Rep. 2018;39:1649–1657. doi: 10.3892/or.2018.6259. PubMed DOI PMC

Malric L., Monferran S., Delmas C., Arnauduc F., Dahan P., Boyrie S., Deshors P., Lubrano V., Da Mota D.F., Gilhodes J., et al. Inhibiting Integrin Beta8 to Differentiate and Radiosensitize Glioblastoma-Initiating Cells. Mol. Cancer Res. 2019;17:384–397. doi: 10.1158/1541-7786.MCR-18-0386. PubMed DOI

Wang W.W., Wang Y.B., Wang D.Q., Lin Z., Sun R.J. Integrin Beta-8 (ITGB8) Silencing Reverses Gefitinib Resistance of Human Hepatic Cancer HepG2/G Cell Line. Int. J. Clin. Exp. Med. 2015;8:3063–3071. PubMed PMC

Lian Y., Cai Z., Gong H., Xue S., Wu D., Wang K. HOTTIP: A Critical Oncogenic Long Non-Coding RNA in Human Cancers. Mol. Biosyst. 2016;12:3247–3253. doi: 10.1039/C6MB00475J. PubMed DOI

Zhang G.J., Song W., Song Y. Overexpression of HOTTIP Promotes Proliferation and Drug Resistance of Lung Adenocarcinoma by Regulating AKT Signaling Pathway. Eur. Rev. Med. Pharmacol. Sci. 2017;21:5683–5690. PubMed

Wang J., Lv B., Su Y., Wang X., Bu J., Yao L. Exosome-Mediated Transfer of lncRNA HOTTIP Promotes Cisplatin Resistance in Gastric Cancer Cells by Regulating HMGA1/miR-218 Axis. Onco Targets Ther. 2019;12:11325–11338. doi: 10.2147/OTT.S231846. PubMed DOI PMC

Li Z., Zhao L., Wang Q. Overexpression of Long Non-Coding RNA HOTTIP Increases Chemoresistance of Osteosarcoma Cell by Activating the Wnt/Beta-Catenin Pathway. Am. J. Transl. Res. 2016;8:2385–2393. PubMed PMC

Parolia A., Crea F., Xue H., Wang Y., Mo F., Ramnarine V.R., Liu H.H., Lin D., Saidy N.R.N., Clermont P., et al. The Long Non-Coding RNA PCGEM1 is Regulated by Androgen Receptor Activity In Vivo. Mol. Cancer. 2015;14:1–7. doi: 10.1186/s12943-015-0314-4. PubMed DOI PMC

Prensner J.R., Sahu A., Iyer M.K., Malik R., Chandler B., Asangani I.A., Poliakov A., Vergara I.A., Alshalalfa M., Jenkins R.B., et al. The IncRNAs PCGEM1 and PRNCR1 are Not Implicated in Castration Resistant Prostate Cancer. Oncotarget. 2014;5:1434–1438. doi: 10.18632/oncotarget.1846. PubMed DOI PMC

Yang L., Lin C., Jin C., Yang J.C., Tanasa B., Li W., Merkurjev D., Ohgi K.A., Meng D., Zhang J., et al. lncRNA-Dependent Mechanisms of Androgen-Receptor-Regulated Gene Activation Programs. Nature. 2013;500:598–602. doi: 10.1038/nature12451. PubMed DOI PMC

Mukhopadhyay N.K., Kim J., Cinar B., Ramachandran A., Hager M.H., Di Vizio D., Adam R.M., Rubin M.A., Raychaudhuri P., De Benedetti A., et al. Heterogeneous Nuclear Ribonucleoprotein K is a Novel Regulator of Androgen Receptor Translation. Cancer Res. 2009;69:2210–2218. doi: 10.1158/0008-5472.CAN-08-2308. PubMed DOI PMC

Li Y., Lv S., Ning H., Li K., Zhou X., Xv H., Wen H. Down-Regulation of CASC2 Contributes to Cisplatin Resistance in Gastric Cancer by Sponging miR-19a. Biomed. Pharmacother. 2018;108:1775–1782. doi: 10.1016/j.biopha.2018.09.181. PubMed DOI

Liao Y., Shen L., Zhao H., Liu Q., Fu J., Guo Y., Peng R., Cheng L. LncRNA CASC2 Interacts with miR-181a to Modulate Glioma Growth and Resistance to TMZ through PTEN Pathway. J. Cell. Biochem. 2017;118:1889–1899. doi: 10.1002/jcb.25910. PubMed DOI

Zheng P., Dong L., Zhang B., Dai J., Zhang Y., Wang Y., Qin S. Long Noncoding RNA CASC2 Promotes Paclitaxel Resistance in Breast Cancer through Regulation of miR-18a-5p/CDK19. Histochem. Cell Biol. 2019;152:281–291. doi: 10.1007/s00418-019-01794-4. PubMed DOI

Feng Y., Zou W., Hu C., Li G., Zhou S., He Y., Ma F., Deng C., Sun L. Modulation of CASC2/miR-21/PTEN Pathway Sensitizes Cervical Cancer to Cisplatin. Arch. Biochem. Biophys. 2017;623–624 doi: 10.1016/j.abb.2017.05.001. PubMed DOI

Tong L., Wu W. Effects of Long Non-Coding RNA (lncRNA) Cancer Susceptibility Candidate 2c (CASC2c) on Proliferation, Metastasis and Drug Resistance of Non-Small Cell Lung Cancer (NSCLC) Cells through ERK1/2 and Beta-Catenin Signaling Pathways. Pathol. Res. Pract. 2019;215:152522. doi: 10.1016/j.prp.2019.152522. PubMed DOI

Zheng H.C. The Molecular Mechanisms of Chemoresistance in Cancers. Oncotarget. 2017;8:59950–59964. doi: 10.18632/oncotarget.19048. PubMed DOI PMC

Park J.S., Kim J., Elghiaty A., Ham W.S. Recent Global Trends in Testicular Cancer Incidence and Mortality. Med. Baltim. 2018;97:e12390. doi: 10.1097/MD.0000000000012390. PubMed DOI PMC

Magers M.J., Idrees M.T. Updates in Staging and Reporting of Testicular Cancer. Surg. Pathol. Clin. 2018;11:813–824. doi: 10.1016/j.path.2018.07.005. PubMed DOI

. International Germ Cell Consensus Classification: A Prognostic Factor-Based Staging System for Metastatic Germ Cell Cancers. International Germ Cell Cancer Collaborative Group. J. Clin. Oncol. 1997;15:594–603. doi: 10.1200/JCO.1997.15.2.594. PubMed DOI

Woldu S.L., Bagrodia A. Update on Epidemiologic Considerations and Treatment Trends in Testicular Cancer. Curr. Opin. Urol. 2018;28:440–447. doi: 10.1097/MOU.0000000000000532. PubMed DOI PMC

Regouc M., Belge G., Lorch A., Dieckmann K.P., Pichler M. Non-Coding microRNAs as Novel Potential Tumor Markers in Testicular Cancer. Cancers. 2020;12:749. doi: 10.3390/cancers12030749. PubMed DOI PMC

Lembeck A.L., Puchas P., Hutterer G., Barth D.A., Terbuch A., Bauernhofer T., Pichler M. MicroRNAs as Appropriate Discriminators in Non-Specific Alpha-Fetoprotein (AFP) Elevation in Testicular Germ Cell Tumor Patients. Noncoding RNA. 2020;6:2. doi: 10.3390/ncrna6010002. PubMed DOI PMC

Raveh E., Matouk I.J., Gilon M., Hochberg A. The H19 Long Non-Coding RNA in Cancer Initiation, Progression and Metastasis—A Proposed Unifying Theory. Mol. Cancer. 2015;14 doi: 10.1186/s12943-015-0458-2. PubMed DOI PMC

Wang Y., Gan Y., Tan Z., Zhou J., Kitazawa R., Jiang X., Tang Y., Yang J. TDRG1 Functions in Testicular Seminoma are Dependent on the PI3K/Akt/mTOR Signaling Pathway. Onco Targets Ther. 2016;9:409–420. PubMed PMC

Gan Y., Wang Y., Tan Z., Zhou J., Kitazawa R., Jiang X., Tang Y., Yang J. TDRG1 Regulates Chemosensitivity of Seminoma TCam-2 Cells to Cisplatin Via PI3K/Akt/mTOR Signaling Pathway and Mitochondria-Mediated Apoptotic Pathway. Cancer. Biol. Ther. 2016;17:741–750. doi: 10.1080/15384047.2016.1178425. PubMed DOI PMC

Zheng Z.G., Xu H., Suo S.S., Xu X.L., Ni M.W., Gu L.H., Chen W., Wang L.Y., Zhao Y., Tian B., et al. The Essential Role of H19 Contributing to Cisplatin Resistance by Regulating Glutathione Metabolism in High-Grade Serous Ovarian Cancer. Sci. Rep. 2016;6:26093. doi: 10.1038/srep26093. PubMed DOI PMC

Wang Q., Cheng N., Li X., Pan H., Li C., Ren S., Su C., Cai W., Zhao C., Zhang L., et al. Correlation of Long Non-Coding RNA H19 Expression with Cisplatin-Resistance and Clinical Outcome in Lung Adenocarcinoma. Oncotarget. 2017;8:2558–2567. doi: 10.18632/oncotarget.13708. PubMed DOI PMC

Jia J., Zhang X., Zhan D., Li J., Li Z., Li H., Qian J. LncRNA H19 Interacted with miR-130a-3p and miR-17-5p to Modify Radio-Resistance and Chemo-Sensitivity of Cardiac Carcinoma Cells. Cancer Med. 2019;8:1604–1618. doi: 10.1002/cam4.1860. PubMed DOI PMC

Wu Y., Zhou Y., He J., Sun H., Jin Z. Long Non-Coding RNA H19 Mediates Ovarian Cancer Cell Cisplatin-Resistance and Migration during EMT. Int. J. Clin. Exp. Pathol. 2019;12:2506–2515. PubMed PMC

Shah M.Y., Ferrajoli A., Sood A.K., Lopez-Berestein G., Calin G.A. microRNA Therapeutics in Cancer—An Emerging Concept. EBioMedicine. 2016;12:34–42. doi: 10.1016/j.ebiom.2016.09.017. PubMed DOI PMC

Dragomir M.P., Kopetz S., Ajani J.A., Calin G.A. Non-Coding RNAs in GI Cancers: From Cancer Hallmarks to Clinical Utility. Gut. 2020;69:748–763. doi: 10.1136/gutjnl-2019-318279. PubMed DOI

De Los Santos M.C., Dragomir M.P., Calin G.A. The Role of Exosomal Long Non-Coding RNAs in Cancer Drug Resistance. Cancer. Drug Resist. 2019;2:1178–1192. doi: 10.20517/cdr.2019.74. PubMed DOI PMC

Pardini B., Sabo A.A., Birolo G., Calin G.A. Noncoding RNAs in Extracellular Fluids as Cancer Biomarkers: The New Frontier of Liquid Biopsies. Cancers. 2019;11:1170. doi: 10.3390/cancers11081170. PubMed DOI PMC