Liquid biopsy-the determination of circulating cells, proteins, DNA or RNA from biofluids through a "less invasive" approach-has emerged as a novel approach in all cancer entities. Circulating non-(protein) coding RNAs including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and YRNAs can be passively released by tissue or cell damage or actively secreted as cell-free circulating RNAs, bound to lipoproteins or carried by exosomes. In renal cell carcinoma (RCC), a growing body of evidence suggests circulating non-coding RNAs (ncRNAs) such as miRNAs, lncRNAs, and YRNAs as promising and easily accessible blood-based biomarkers for the early diagnosis of RCC as well as for the prediction of prognosis and treatment response. In addition, circulating ncRNAs could also play a role in RCC pathogenesis and progression. This review gives an overview over the current study landscape of circulating ncRNAs and their involvement in RCC pathogenesis as well as their potential utility as future biomarkers in RCC diagnosis and treatment.

Central European Institute of Technology Masaryk University Brno Czechia

Department of Comprehensive Cancer Care Masaryk Memorial Cancer Institute Brno Czechia

Department of Experimental Therapeutics The University of Texas MD Anderson Cancer Center Houston TX United States

Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer Center Houston TX United States

Department of Tumor Biology Center of Experimental Medicine University Medical Center Hamburg Eppendorf Hamburg Germany

Research Centre for Functional Genomics and Translational Medicine Iuliu Hatieganu University of Medicine and Pharmacy Cluj Napoca Romania

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

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Arroyo J. D., Chevillet J. R., Kroh E. M., Ruf I. K., Pritchard C. C., Gibson D. F., et al. (2011). Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc. Natl. Acad. Sci. U.S.A. 108 5003–5008. 10.1073/pnas.1019055108 PubMed DOI PMC

Bai M., Zou B., Wang Z., Li P., Wang H., Ou Y., et al. (2018). Comparison of two detection systems for circulating tumor cells among patients with renal cell carcinoma. Int. Urol. Nephrol. 50 1801–1809. 10.1007/s11255-018-1954-2 PubMed DOI

Bao X., Duan J., Yan Y., Ma X., Zhang Y., Wang H., et al. (2017). Upregulation of long noncoding RNA PVT1 predicts unfavorable prognosis in patients with clear cell renal cell carcinoma. Cancer Biomark 21 55–63. 10.3233/cbm-170251 PubMed DOI

Bartel D. P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116 281–297. PubMed

Barth D. A., Slaby O., Klec C., Juracek J., Drula R., Calin G. A., et al. (2019). Current concepts of non-coding RNAs in the pathogenesis of non-clear cell renal cell carcinoma. Cancers (Basel) 11:10.3390/cancers11101580. PubMed PMC

Bergerot P. G., Hahn A. W., Bergerot C. D., Jones J., Pal S. K. (2018). The role of circulating tumor DNA in renal cell carcinoma. Curr. Treat. Options Oncol. 19:10. PubMed

Bryzgunova O. E., Laktionov P. P. (2015). Extracellular nucleic acids in urine: sources, structure, diagnostic potential. Acta Naturae 7 48–54. 10.32607/20758251-2015-7-3-48-54 PubMed DOI PMC

Bu J., Nair A., Kubiatowicz L. J., Poellmann M. J., Jeong W. J., Reyes-Martinez M., et al. (2020). Surface engineering for efficient capture of circulating tumor cells in renal cell carcinoma: From nanoscale analysis to clinical application. Biosens. Bioelectron. 162:112250. 10.1016/j.bios.2020.112250 PubMed DOI PMC

Butz H., Nofech-Mozes R., Ding Q., Khella H. W. Z., Szabo P. M., Jewett M., et al. (2016). Exosomal MicroRNAs are diagnostic biomarkers and can mediate cell-cell communication in renal cell carcinoma. Eur. Urol. Focus 2 210–218. 10.1016/j.euf.2015.11.006 PubMed DOI

Cella D., Grunwald V., Escudier B., Hammers H. J., George S., Nathan P., et al. (2019). Patient-reported outcomes of patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab versus sunitinib (CheckMate 214): a randomised, phase 3 trial. Lancet Oncol. 20 297–310. 10.1016/s1470-2045(18)30778-2 PubMed DOI PMC

Chan J. K., Kiet T. K., Blansit K., Ramasubbaiah R., Hilton J. F., Kapp D. S., et al. (2014). MiR-378 as a biomarker for response to anti-angiogenic treatment in ovarian cancer. Gynecol. Oncol. 133 568–574. 10.1016/j.ygyno.2014.03.564 PubMed DOI

Chanudet E., Wozniak M. B., Bouaoun L., Byrnes G., Mukeriya A., Zaridze D., et al. (2017). Large-scale genome-wide screening of circulating microRNAs in clear cell renal cell carcinoma reveals specific signatures in late-stage disease. Int. J. Cancer 141 1730–1740. 10.1002/ijc.30845 PubMed DOI

Chen Q. G., Zhou W., Han T., Du S. Q., Li Z. H., Zhang Z., et al. (2016). MiR-378 suppresses prostate cancer cell growth through downregulation of MAPK1 in vitro and in vivo. Tumour Biol. 37 2095–2103. 10.1007/s13277-015-3996-8 PubMed DOI

Chen X., Lou N., Ruan A., Qiu B., Yan Y., Wang X., et al. (2018a). miR-224/miR-141 ratio as a novel diagnostic biomarker in renal cell carcinoma. Oncol. Lett. 16 1666–1674. PubMed PMC

Chen X., Xu X., Pan B., Zeng K., Xu M., Liu X., et al. (2018b). miR-150-5p suppresses tumor progression by targeting VEGFA in colorectal cancer. Aging (Albany NY) 10 3421–3437. 10.18632/aging.101656 PubMed DOI PMC

Cheng T., Wang L., Li Y., Huang C., Zeng L., Yang J. (2013). Differential microRNA expression in renal cell carcinoma. Oncol. Lett. 6 769–776. 10.3892/ol.2013.1460 PubMed DOI PMC

Chi Y., Wang D., Wang J., Yu W., Yang J. (2019). Long non-coding RNA in the pathogenesis of cancers. Cells 8:1015. 10.3390/cells8091015 PubMed DOI PMC

Chirshev E., Oberg K. C., Ioffe Y. J., Unternaehrer J. J. (2019). Let-7 as biomarker, prognostic indicator, and therapy for precision medicine in cancer. Clin. Transl. Med. 8:24. PubMed PMC

Cimadamore A., Gasparrini S., Massari F., Santoni M., Cheng L., Lopez-Beltran A., et al. (2019). Emerging molecular technologies in renal cell carcinoma: liquid biopsy. Cancers (Basel) 11:196. 10.3390/cancers11020196 PubMed DOI PMC

Colombo M., Moita C., van Niel G., Kowal J., Vigneron J., Benaroch P., et al. (2013). Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. J. Cell. Sci. 126(Pt 24) 5553–5565. 10.1242/jcs.128868 PubMed DOI

Cortez M. A., Bueso-Ramos C., Ferdin J., Lopez-Berestein G., Sood A. K., Calin G. A. (2011). MicroRNAs in body fluids–the mix of hormones and biomarkers. Nat. Rev. Clin. Oncol. 8 467–477. 10.1038/nrclinonc.2011.76 PubMed DOI PMC

Dalpiaz O., Luef T., Seles M., Stotz M., Stojakovic T., Pummer K., et al. (2017). Critical evaluation of the potential prognostic value of the pretreatment-derived neutrophil-lymphocyte ratio under consideration of C-reactive protein levels in clear cell renal cell carcinoma. Br. J. Cancer 116 85–90. 10.1038/bjc.2016.393 PubMed DOI PMC

Dang K., Myers K. A. (2015). The role of hypoxia-induced miR-210 in cancer progression. Int. J. Mol. Sci. 16 6353–6372. 10.3390/ijms16036353 PubMed DOI PMC

Derderian C., Orunmuyi A. T., Olapade-Olaopa E. O., Ogunwobi O. O. (2019). PVT1 signaling is a mediator of cancer progression. Front. Oncol. 9:502. 10.3389/fonc.2019.00502 PubMed DOI PMC

Dhahbi J. M., Spindler S. R., Atamna H., Boffelli D., Martin D. I. (2014). Deep sequencing of serum small RNAs identifies patterns of 5’ tRNA half and YRNA fragment expression associated with breast cancer. Biomark Cancer 6 37–47. PubMed PMC

Dhahbi J. M., Spindler S. R., Atamna H., Boffelli D., Mote P., Martin D. I. (2013). 5’-YRNA fragments derived by processing of transcripts from specific YRNA genes and pseudogenes are abundant in human serum and plasma. Physiol. Genomics 45 990–998. 10.1152/physiolgenomics.00129.2013 PubMed DOI

Dias F., Teixeira A. L., Ferreira M., Adem B., Bastos N., Vieira J., et al. (2017). Plasmatic miR-210, miR-221 and miR-1233 profile: potential liquid biopsies candidates for renal cell carcinoma. Oncotarget 8 103315–103326. 10.18632/oncotarget.21733 PubMed DOI PMC

Dieckmann K. P., Radtke A., Geczi L., Matthies C., Anheuser P., Eckardt U., et al. (2019). Serum levels of MicroRNA-371a-3p (M371 Test) as a new biomarker of testicular germ cell tumors: results of a prospective multicentric study. J. Clin. Oncol. 37 1412–1423. 10.1200/jco.18.01480 PubMed DOI PMC

Du M., Giridhar K. V., Tian Y., Tschannen M. R., Zhu J., Huang C. C., et al. (2017). Plasma exosomal miRNAs-based prognosis in metastatic kidney cancer. Oncotarget 8 63703–63714. 10.18632/oncotarget.19476 PubMed DOI PMC

Ellinger J., Gevensleben H., Muller S. C., Dietrich D. (2016). The emerging role of non-coding circulating RNA as a biomarker in renal cell carcinoma. Expert Rev. Mol. Diagn. 16 1059–1065. 10.1080/14737159.2016.1239531 PubMed DOI

Faragalla H., Youssef Y. M., Scorilas A., Khalil B., White N. M., Mejia-Guerrero S., et al. (2012). The clinical utility of miR-21 as a diagnostic and prognostic marker for renal cell carcinoma. J. Mol. Diagn. 14 385–392. 10.1016/j.jmoldx.2012.02.003 PubMed DOI

Farber N. J., Kim C. J., Modi P. K., Hon J. D., Sadimin E. T., Singer E. A. (2017). Renal cell carcinoma: the search for a reliable biomarker. Transl. Cancer Res. 6 620–632. PubMed PMC

Fedorko M., Stanik M., Iliev R., Redova-Lojova M., Machackova T., Svoboda M., et al. (2015). Combination of MiR-378 and MiR-210 serum levels enables sensitive detection of renal cell carcinoma. Int. J. Mol. Sci. 16 23382–23389. 10.3390/ijms161023382 PubMed DOI PMC

Ferlay J., Soerjomataram I., Dikshit R., Eser S., Mathers C., Rebelo M., et al. (2015). Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer 136 E359–E386. PubMed

Fujii N., Hirata H., Ueno K., Mori J., Oka S., Shimizu K., et al. (2017). Extracellular miR-224 as a prognostic marker for clear cell renal cell carcinoma. Oncotarget 8 109877–109888. 10.18632/oncotarget.22436 PubMed DOI PMC

Gallo A., Tandon M., Alevizos I., Illei G. G. (2012). The majority of microRNAs detectable in serum and saliva is concentrated in exosomes. PLoS One 7:e30679. 10.1371/journal.pone.0030679 PubMed DOI PMC

Gamez-Pozo A., Anton-Aparicio L. M., Bayona C., Borrega P., Gallegos Sancho M. I., Garcia-Dominguez R., et al. (2012). MicroRNA expression profiling of peripheral blood samples predicts resistance to first-line sunitinib in advanced renal cell carcinoma patients. Neoplasia 14 1144–1152. PubMed PMC

Garcia-Donas J., Beuselinck B., Inglada-Perez L., Grana O., Schoffski P., Wozniak A., et al. (2016). Deep sequencing reveals microRNAs predictive of antiangiogenic drug response. JCI Insight 1:e86051. PubMed PMC

Gowrishankar B., Ibragimova I., Zhou Y., Slifker M. J., Devarajan K., Al-Saleem T., et al. (2014). MicroRNA expression signatures of stage, grade, and progression in clear cell RCC. Cancer Biol. Ther. 15 329–341. 10.4161/cbt.27314 PubMed DOI PMC

Groot M., Lee H. (2020). Sorting mechanisms for MicroRNAs into extracellular vesicles and their associated diseases. Cells 9:1044. 10.3390/cells9041044 PubMed DOI PMC

Guan Y., Gong Z., Xiao T., Li Z. (2018). Knockdown of miR-572 suppresses cell proliferation and promotes apoptosis in renal cell carcinoma cells by targeting the NF2/Hippo signaling pathway. Int. J. Clin. Exp. Pathol. 11 5705–5714. PubMed PMC

Guo S. J., Zeng H. X., Huang P., Wang S., Xie C. H., Li S. J. (2018). MiR-508-3p inhibits cell invasion and epithelial-mesenchymal transition by targeting ZEB1 in triple-negative breast cancer. Eur. Rev. Med. Pharmacol. Sci. 22 6379–6385. PubMed

Gurunathan S., Kang M. H., Jeyaraj M., Qasim M., Kim J. H. (2019). Review of the isolation, characterization, biological function, and multifarious therapeutic approaches of exosomes. Cells 8:307. 10.3390/cells8040307 PubMed DOI PMC

Han L., Wang B., Wang R., Wang Z., Gong S., Chen G., et al. (2019). Prognostic and clinicopathological significance of long non-coding RNA PANDAR expression in cancer patients: a meta-analysis. Front. Oncol. 9:1337. 10.3389/fonc.2019.01337 PubMed DOI PMC

Hauser S., Wulfken L. M., Holdenrieder S., Moritz R., Ohlmann C. H., Jung V., et al. (2012). Analysis of serum microRNAs (miR-26a-2∗, miR-191, miR-337-3p and miR-378) as potential biomarkers in renal cell carcinoma. Cancer Epidemiol. 36 391–394. 10.1016/j.canep.2012.04.001 PubMed DOI

He J., He J., Min L., He Y., Guan H., Wang J., et al. (2020). Extracellular vesicles transmitted miR-31-5p promotes sorafenib resistance by targeting MLH1 in renal cell carcinoma. Int. J. Cancer 146 1052–1063. 10.1002/ijc.32543 PubMed DOI

He Z. H., Qin X. H., Zhang X. L., Yi J. W., Han J. Y. (2018). Long noncoding RNA GIHCG is a potential diagnostic and prognostic biomarker and therapeutic target for renal cell carcinoma. Eur. Rev. Med. Pharmacol. Sci. 22 46–54. PubMed

Hendrick J. P., Wolin S. L., Rinke J., Lerner M. R., Steitz J. A. (1981). Ro small cytoplasmic ribonucleoproteins are a subclass of La ribonucleoproteins: further characterization of the Ro and La small ribonucleoproteins from uninfected mammalian cells. Mol. Cell. Biol. 1 1138–1149. 10.1128/mcb.1.12.1138 PubMed DOI PMC

Heng D. Y., Xie W., Regan M. M., Warren M. A., Golshayan A. R., Sahi C., et al. (2009). Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J. Clin. Oncol. 27 5794–5799. 10.1200/jco.2008.21.4809 PubMed DOI

Hosseini M., Khatamianfar S., Hassanian S. M., Nedaeinia R., Shafiee M., Maftouh M., et al. (2017). Exosome-encapsulated microRNAs as potential circulating biomarkers in colon cancer. Curr. Pharm. Des. 23 1705–1709. 10.2174/1381612822666161201144634 PubMed DOI

Huang T., Kang W., Zhang B., Wu F., Dong Y., Tong J. H., et al. (2016). miR-508-3p concordantly silences NFKB1 and RELA to inactivate canonical NF-kappaB signaling in gastric carcinogenesis. Mol. Cancer 15:9. PubMed PMC

Huang W., Zhao M., Wei N., Wang X., Cao H., Du Q., et al. (2014). Site-specific RNase A activity was dramatically reduced in serum from multiple types of cancer patients. PLoS One 9:e96490. 10.1371/journal.pone.0096490 PubMed DOI PMC

Iwamoto H., Kanda Y., Sejima T., Osaki M., Okada F., Takenaka A. (2014). Serum miR-210 as a potential biomarker of early clear cell renal cell carcinoma. Int. J. Oncol. 44 53–58. 10.3892/ijo.2013.2169 PubMed DOI

Janzen N. K., Kim H. L., Figlin R. A., Belldegrun A. S. (2003). Surveillance after radical or partial nephrectomy for localized renal cell carcinoma and management of recurrent disease. Urol. Clin. North Am. 30 843–852. 10.1016/s0094-0143(03)00056-9 PubMed DOI

Javidi M. A., Ahmadi A. H., Bakhshinejad B., Nouraee N., Babashah S., Sadeghizadeh M. (2014). Cell-free microRNAs as cancer biomarkers: the odyssey of miRNAs through body fluids. Med. Oncol. 31:295. PubMed

Jiang N., Pan J., Fang S., Zhou C., Han Y., Chen J., et al. (2019). Liquid biopsy: Circulating exosomal long noncoding RNAs in cancer. Clin. Chim. Acta 495 331–337. 10.1016/j.cca.2019.04.082 PubMed DOI

Jiang X., Li Q., Zhang S., Song C., Zheng P. (2019). Long noncoding RNA GIHCG induces cancer progression and chemoresistance and indicates poor prognosis in colorectal cancer. Onco Targets Ther. 12 1059–1070. 10.2147/ott.s192290 PubMed DOI PMC

Khella H. W. Z., Butz H., Ding Q., Rotondo F., Evans K. R., Kupchak P., et al. (2015). miR-221/222 are involved in response to sunitinib treatment in metastatic renal cell carcinoma. Mol. Ther. 23 1748–1758. 10.1038/mt.2015.129 PubMed DOI PMC

Ko J. J., Xie W., Kroeger N., Lee J. L., Rini B. I., Knox J. J., et al. (2015). The international metastatic renal cell carcinoma database consortium model as a prognostic tool in patients with metastatic renal cell carcinoma previously treated with first-line targeted therapy: a population-based study. Lancet Oncol. 16 293–300. 10.1016/s1470-2045(14)71222-7 PubMed DOI

Koczera P., Martin L., Marx G., Schuerholz T. (2016). The Ribonuclease A superfamily in humans: canonical RNases as the buttress of innate immunity. Int. J. Mol. Sci. 17:1278. 10.3390/ijms17081278 PubMed DOI PMC

Krebs M., Solimando A. G., Kalogirou C., Marquardt A., Frank T., Sokolakis I., et al. (2020). miR-221-3p regulates VEGFR2 expression in high-risk prostate cancer and represents an escape mechanism from sunitinib In Vitro. J. Clin. Med. 9:670. 10.3390/jcm9030670 PubMed DOI PMC

Krist B., Florczyk U., Pietraszek-Gremplewicz K., Jozkowicz A., Dulak J. (2015). The role of miR-378a in metabolism, angiogenesis, and muscle biology. Int. J. Endocrinol. 2015:281756. PubMed PMC

Kulkarni B., Kirave P., Gondaliya P., Jash K., Jain A., Tekade R. K., et al. (2019). Exosomal miRNA in chemoresistance, immune evasion, metastasis and progression of cancer. Drug Discov. Today 24 2058–2067. 10.1016/j.drudis.2019.06.010 PubMed DOI

Lee D. Y., Deng Z., Wang C. H., Yang B. B. (2007). MicroRNA-378 promotes cell survival, tumor growth, and angiogenesis by targeting SuFu and Fus-1 expression. Proc. Natl. Acad. Sci. U.S.A. 104 20350–20355. 10.1073/pnas.0706901104 PubMed DOI PMC

Lee I., Baxter D., Lee M. Y., Scherler K., Wang K. (2017). The importance of standardization on analyzing circulating RNA. Mol. Diagn. Ther. 21 259–268. 10.1007/s40291-016-0251-y PubMed DOI PMC

Lee S. P., Hsieh P. L., Fang C. Y., Chu P. M., Liao Y. W., Yu C. H., et al. (2020). LINC00963 promotes cancer stemness, metastasis, and drug resistance in head and neck carcinomas via ABCB5 regulation. Cancers (Basel) 12:10.3390/cancers12051073. PubMed PMC

Li G., Zhao A., Peoch M., Cottier M., Mottet N. (2017). Detection of urinary cell-free miR-210 as a potential tool of liquid biopsy for clear cell renal cell carcinoma. Urol. Oncol. 35 294–299. 10.1016/j.urolonc.2016.12.007 PubMed DOI

Li H., Ouyang R., Wang Z., Zhou W., Chen H., Jiang Y., et al. (2016). MiR-150 promotes cellular metastasis in non-small cell lung cancer by targeting FOXO4. Sci. Rep. 6:39001. PubMed PMC

Li H. C., Li J. P., Wang Z. M., Fu D. L., Li Z. L., Zhang D., et al. (2014). Identification of angiogenesis-related miRNAs in a population of patients with renal clear cell carcinoma. Oncol. Rep. 32 2061–2069. 10.3892/or.2014.3403 PubMed DOI

Li J., Li Z., Zheng W., Li X., Wang Z., Cui Y., et al. (2017). PANDAR: a pivotal cancer-related long non-coding RNA in human cancers. Mol. Biosyst. 13 2195–2201. 10.1039/c7mb00414a PubMed DOI

Li S., Yang F., Wang M., Cao W., Yang Z. (2017). miR-378 functions as an onco-miRNA by targeting the ST7L/Wnt/β-catenin pathway in cervical cancer. Int. J. Mol. Med. 40 1047–1056. 10.3892/ijmm.2017.3116 PubMed DOI PMC

Li W., Zheng Z., Chen H., Cai Y., Xie W. (2018). Knockdown of long non-coding RNA PVT1 induces apoptosis and cell cycle arrest in clear cell renal cell carcinoma through the epidermal growth factor receptor pathway. Oncol. Lett. 15 7855–7863. PubMed PMC

Li X., Xin S., He Z., Che X., Wang J., Xiao X., et al. (2014). MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor PDCD4 and promotes cell transformation, proliferation, and metastasis in renal cell carcinoma. Cell Physiol. Biochem. 33 1631–1642. 10.1159/000362946 PubMed DOI

Li Y., Quan J., Chen F., Pan X., Zhuang C., Xiong T., et al. (2019). MiR-31-5p acts as a tumor suppressor in renal cell carcinoma by targeting cyclin-dependent kinase 1 (CDK1). Biomed. Pharmacother. 111 517–526. 10.1016/j.biopha.2018.12.102 PubMed DOI

Li Y., Ye Y., Feng B., Qi Y. (2017). Long noncoding RNA lncARSR promotes doxorubicin resistance in hepatocellular carcinoma via modulating PTEN-PI3K/Akt pathway. J. Cell. Biochem. 118 4498–4507. 10.1002/jcb.26107 PubMed DOI

Liu F., Chen N., Xiao R., Wang W., Pan Z. (2016). miR-144-3p serves as a tumor suppressor for renal cell carcinoma and inhibits its invasion and metastasis by targeting MAP3K8. Biochem. Biophys. Res. Commun. 480 87–93. 10.1016/j.bbrc.2016.10.004 PubMed DOI

Liu G., Jiang Z., Qiao M., Wang F. (2019). Lnc-GIHCG promotes cell proliferation and migration in gastric cancer through miR- 1281 adsorption. Mol. Genet. Genomic Med. 7:e711. 10.1002/mgg3.711 PubMed DOI PMC

Liu L., Li Y., Liu S., Duan Q., Chen L., Wu T., et al. (2017). Downregulation of miR-193a-3p inhibits cell growth and migration in renal cell carcinoma by targeting PTEN. Tumour Biol. 39:1010428317711951. PubMed

Liu L. L., Li D., He Y. L., Zhou Y. Z., Gong S. H., Wu L. Y., et al. (2017). miR-210 protects renal cell against hypoxia-induced apoptosis by targeting HIF-1 alpha. Mol. Med. 23 258–271. 10.2119/molmed.2017.00013 PubMed DOI PMC

Liu S., Deng X., Zhang J. (2019a). Identification of dysregulated serum miR-508-3p and miR-885-5p as potential diagnostic biomarkers of clear cell renal carcinoma. Mol. Med. Rep. 20 5075–5083. PubMed PMC

Liu S., Wang Y., Li W., Yu S., Wen Z., Chen Z., et al. (2019b). miR-221-5p acts as an oncogene and predicts worse survival in patients of renal cell cancer. Biomed. Pharmacother. 119:109406. 10.1016/j.biopha.2019.109406 PubMed DOI

Liu T. Y., Zhang H., Du S. M., Li J., Wen X. H. (2016). Expression of microRNA-210 in tissue and serum of renal carcinoma patients and its effect on renal carcinoma cell proliferation, apoptosis, and invasion. Genet. Mol. Res. 15:15017746. PubMed

Liu X. G., Zhu W. Y., Huang Y. Y., Ma L. N., Zhou S. Q., Wang Y. K., et al. (2012). High expression of serum miR-21 and tumor miR-200c associated with poor prognosis in patients with lung cancer. Med. Oncol. 29 618–626. 10.1007/s12032-011-9923-y PubMed DOI

Lou N., Ruan A. M., Qiu B., Bao L., Xu Y. C., Zhao Y., et al. (2017). miR-144-3p as a novel plasma diagnostic biomarker for clear cell renal cell carcinoma. Urol. Oncol. 35 36.e7–36.e14. 10.1016/j.urolonc.2016.07.012 PubMed DOI

Lu G. J., Dong Y. Q., Zhang Q. M., Di W. Y., Jiao L. Y., Gao Q. Z., et al. (2015). miRNA-221 promotes proliferation, migration and invasion by targeting TIMP2 in renal cell carcinoma. Int. J. Clin. Exp. Pathol. 8 5224–5229. PubMed PMC

Lv J., Zhu Y., Zhang Q. (2020). An increased level of MiR-222-3p is associated with TMP2 suppression, ERK activation and is associated with metastasis and a poor prognosis in renal clear cell carcinoma. Cancer Biomark. 28 141–149. 10.3233/cbm-190264 PubMed DOI

Ma J., Wu D., Yi J., Yi Y., Zhu X., Qiu H., et al. (2019). MiR-378 promoted cell proliferation and inhibited apoptosis by enhanced stem cell properties in chronic myeloid leukemia K562 cells. Biomed. Pharmacother. 112:108623. 10.1016/j.biopha.2019.108623 PubMed DOI

Ma Y., Zhang H., He X., Song H., Qiang Y., Li Y., et al. (2015). miR-106a∗ inhibits the proliferation of renal carcinoma cells by targeting IRS-2. Tumour Biol. 36 8389–8398. 10.1007/s13277-015-3605-x PubMed DOI

Mathur R. (2018). ARID1A loss in cancer: Towards a mechanistic understanding. Pharmacol. Ther. 190 15–23. 10.1016/j.pharmthera.2018.05.001 PubMed DOI

McCormick R. I., Blick C., Ragoussis J., Schoedel J., Mole D. R., Young A. C., et al. (2013). miR-210 is a target of hypoxia-inducible factors 1 and 2 in renal cancer, regulates ISCU and correlates with good prognosis. Br. J. Cancer 108 1133–1142. 10.1038/bjc.2013.56 PubMed DOI PMC

Motzer R. J., Escudier B., McDermott D. F., George S., Hammers H. J., Srinivas S., et al. (2015). Nivolumab versus everolimus in advanced renal-cell carcinoma. N. Engl. J. Med. 373 1803–1813. PubMed PMC

Motzer R. J., Tannir N. M., McDermott D. F., Aren Frontera O., Melichar B., Choueiri T. K., et al. (2018). Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N. Engl. J. Med. 378 1277–1290. PubMed PMC

Nandagopal L., Sonpavde G. (2016). Circulating biomarkers in bladder cancer. Bladder Cancer 2 369–379. 10.3233/blc-160075 PubMed DOI PMC

Neal C. S., Michael M. Z., Rawlings L. H., Van der Hoek M. B., Gleadle J. M. (2010). The VHL-dependent regulation of microRNAs in renal cancer. BMC Med. 8:64. 10.1186/1741-7015-8-64 PubMed DOI PMC

Nientiedt M., Schmidt D., Kristiansen G., Muller S. C., Ellinger J. (2018). YRNA expression profiles are altered in clear cell renal cell carcinoma. Eur. Urol. Focus 4 260–266. 10.1016/j.euf.2016.08.004 PubMed DOI

Novikova I. V., Hennelly S. P., Sanbonmatsu K. Y. (2013). Tackling structures of long noncoding RNAs. Int. J. Mol. Sci. 14 23672–23684. 10.3390/ijms141223672 PubMed DOI PMC

Okita K., Hatakeyama S., Tanaka T., Ikehata Y., Tanaka T., Fujita N., et al. (2019). Impact of disagreement between two risk group models on prognosis in patients with metastatic renal-cell carcinoma. Clin. Genitourin. Cancer 17 e440–e446. 10.1016/j.clgc.2019.01.006 PubMed DOI

Palsdottir H. B., Hardarson S., Petursdottir V., Jonsson A., Jonsson E., Sigurdsson M. I., et al. (2012). Incidental detection of renal cell carcinoma is an independent prognostic marker: results of a long-term, whole population study. J. Urol. 187 48–53. 10.1016/j.juro.2011.09.025 PubMed DOI

Pan X., Li Z., Zhao L., Quan J., Zhou L., Xu J., et al. (2018a). microRNA-572 functions as an oncogene and a potential biomarker for renal cell carcinoma prognosis. Oncol. Rep. 40 3092–3101. PubMed

Pan X., Zheng G., Gao C. (2018b). LncRNA PVT1: a novel therapeutic target for cancers. Clin. Lab. 64 655–662. PubMed

Pan Y., Hu J., Ma J., Qi X., Zhou H., Miao X., et al. (2018). MiR-193a-3p and miR-224 mediate renal cell carcinoma progression by targeting alpha-2,3-sialyltransferase IV and the phosphatidylinositol 3 kinase/Akt pathway. Mol. Carcinog. 57 1067–1077. 10.1002/mc.22826 PubMed DOI

Pan Y. J., Wei L. L., Wu X. J., Huo F. C., Mou J., Pei D. S. (2017). MiR-106a-5p inhibits the cell migration and invasion of renal cell carcinoma through targeting PAK5. Cell Death Dis. 8:e3155. 10.1038/cddis.2017.561 PubMed DOI PMC

Peng J., Mo R., Ma J., Fan J. (2015). Let-7b and Let-7c are determinants of intrinsic chemoresistance in renal cell carcinoma. World J. Surg. Oncol. 13:175. PubMed PMC

Penolazzi L., Bonaccorsi G., Gafa R., Ravaioli N., Gabriele D., Bosi C., et al. (2019). SLUG/HIF1-alpha/miR-221 regulatory circuit in endometrial cancer. Gene 711:143938. 10.1016/j.gene.2019.06.028 PubMed DOI

Petrozza V., Carbone A., Bellissimo T., Porta N., Palleschi G., Pastore A. L., et al. (2015). Oncogenic MicroRNAs characterization in clear cell renal cell carcinoma. Int. J. Mol. Sci. 16 29219–29225. PubMed PMC

Pichler M., Rodriguez-Aguayo C., Nam S. Y., Dragomir M. P., Bayraktar R., Anfossi S., et al. (2020). Therapeutic potential of FLANC, a novel primate-specific long non-coding RNA in colorectal cancer. Gut 10.1136/gutjnl-2019-318903 [Epub ahead of print]. PubMed DOI PMC

Powles T., Albiges L., Staehler M., Bensalah K., Dabestani S., Giles R. H., et al. (2017). Updated European association of urology guidelines recommendations for the treatment of first-line metastatic clear cell renal cancer. Eur. Urol. 73 311–315. 10.1016/j.eururo.2017.11.016 PubMed DOI

Pruijn G. J., Wingens P. A., Peters S. L., Thijssen J. P., van Venrooij W. J. (1993). Ro RNP associated Y RNAs are highly conserved among mammals. Biochim. Biophys. Acta 1216 395–401. 10.1016/0167-4781(93)90006-y PubMed DOI

Qin M. M., Chai X., Huang H. B., Feng G., Li X. N., Zhang J., et al. (2019). let-7i inhibits proliferation and migration of bladder cancer cells by targeting HMGA1. BMC Urol. 19:53. 10.1186/s12894-019-0485-1 PubMed DOI PMC

Qu L., Ding J., Chen C., Wu Z. J., Liu B., Gao Y., et al. (2016). Exosome-transmitted lncARSR promotes sunitinib resistance in renal cancer by acting as a competing endogenous RNA. Cancer Cell 29 653–668. 10.1016/j.ccell.2016.03.004 PubMed DOI

Redova M., Poprach A., Nekvindova J., Iliev R., Radova L., Lakomy R., et al. (2012). Circulating miR-378 and miR-451 in serum are potential biomarkers for renal cell carcinoma. J. Transl. Med. 10:55. 10.1186/1479-5876-10-55 PubMed DOI PMC

Rini B. I., Campbell S. C., Escudier B. (2009). Renal cell carcinoma. Lancet 373 1119–1132. PubMed

Rini B. I., Plimack E. R., Stus V., Gafanov R., Hawkins R., Nosov D., et al. (2019). Pembrolizumab plus Axitinib versus Sunitinib for advanced renal-cell carcinoma. N. Engl. J. Med. 380 1116–1127. PubMed

Rossi S. H., Klatte T., Usher-Smith J., Stewart G. D. (2018). Epidemiology and screening for renal cancer. World J. Urol. 36 1341–1353. PubMed PMC

Sanders I., Holdenrieder S., Walgenbach-Brunagel G., von Ruecker A., Kristiansen G., Muller S. C., et al. (2012). Evaluation of reference genes for the analysis of serum miRNA in patients with prostate cancer, bladder cancer and renal cell carcinoma. Int. J. Urol. 19 1017–1025. 10.1111/j.1442-2042.2012.03082.x PubMed DOI

Schanza L. M., Seles M., Stotz M., Fosselteder J., Hutterer G. C., Pichler M., et al. (2017). MicroRNAs associated with von hippel-lindau pathway in renal cell carcinoma: a comprehensive review. Int. J. Mol. Sci. 18:10.3390/ijms18112495. PubMed PMC

Schwarzenbach H., Milde-Langosch K., Steinbach B., Muller V., Pantel K. (2012). Diagnostic potential of PTEN-targeting miR-214 in the blood of breast cancer patients. Breast Cancer Res. Treat. 134 933–941. 10.1007/s10549-012-1988-6 PubMed DOI

Schwarzenbacher D., Klec C., Pasculli B., Cerk S., Rinner B., Karbiener M., et al. (2019). MiR-1287-5p inhibits triple negative breast cancer growth by interaction with phosphoinositide 3-kinase CB, thereby sensitizing cells for PI3Kinase inhibitors. Breast Cancer Res. 21:20. PubMed PMC

Seles M., Posch F., Pichler G. P., Gary T., Pummer K., Zigeuner R., et al. (2017). Blood platelet volume represents a novel prognostic factor in patients with nonmetastatic renal cell carcinoma and improves the predictive ability of established prognostic scores. J. Urol. 198 1247–1252. 10.1016/j.juro.2017.07.036 PubMed DOI

Shen C., Kaelin W. G., Jr. (2013). The VHL/HIF axis in clear cell renal carcinoma. Semin. Cancer Biol. 23 18–25. 10.1016/j.semcancer.2012.06.001 PubMed DOI PMC

Shen P., Cheng Y. (2020). Long noncoding RNA lncARSR confers resistance to Adriamycin and promotes osteosarcoma progression. Cell Death Dis. 11:362. PubMed PMC

Siegel R. L., Miller K. D., Jemal A. (2019). Cancer statistics, 2019. CA Cancer J. Clin. 69 7–34. PubMed

Smith C. G., Moser T., Mouliere F., Field-Rayner J., Eldridge M., Riediger A. L., et al. (2020). Comprehensive characterization of cell-free tumor DNA in plasma and urine of patients with renal tumors. Genome Med. 12:23. PubMed PMC

Song M. S., Salmena L., Pandolfi P. P. (2012). The functions and regulation of the PTEN tumour suppressor. Nat. Rev. Mol. Cell. Biol. 13 283–296. 10.1038/nrm3330 PubMed DOI

Squadrito M. L., Baer C., Burdet F., Maderna C., Gilfillan G. D., Lyle R., et al. (2014). Endogenous RNAs modulate microRNA sorting to exosomes and transfer to acceptor cells. Cell Rep. 8 1432–1446. 10.1016/j.celrep.2014.07.035 PubMed DOI

Su Y. J., Yu J., Huang Y. Q., Yang J. (2015). Circulating long noncoding RNA as a potential target for prostate cancer. Int. J. Mol. Sci. 16 13322–13338. 10.3390/ijms160613322 PubMed DOI PMC

Sui C. J., Zhou Y. M., Shen W. F., Dai B. H., Lu J. J., Zhang M. F., et al. (2016). Long noncoding RNA GIHCG promotes hepatocellular carcinoma progression through epigenetically regulating miR-200b/a/429. J. Mol. Med. (Berl) 94 1281–1296. 10.1007/s00109-016-1442-z PubMed DOI

Sun J., Jiang Z., Li Y., Wang K., Chen X., Liu G. (2019). Downregulation of miR-21 inhibits the malignant phenotype of pancreatic cancer cells by targeting VHL. Onco Targets Ther. 12 7215–7226. 10.2147/ott.s211535 PubMed DOI PMC

Svoronos A. A., Engelman D. M., Slack F. J. (2016). OncomiR or tumor suppressor? The duplicity of MicroRNAs in cancer. Cancer Res. 76 3666–3670. 10.1158/0008-5472.can-16-0359 PubMed DOI PMC

Tanaka N., Mizuno R., Ito K., Shirotake S., Yasumizu Y., Masunaga A., et al. (2016). External validation of the MSKCC and IMDC risk models in patients treated with targeted therapy as a first-line and subsequent second-line treatment: a Japanese multi-institutional study. Eur. Urol. Focus 2 303–309. 10.1016/j.euf.2015.11.001 PubMed DOI

Teixeira A. L., Ferreira M., Silva J., Gomes M., Dias F., Santos J. I., et al. (2014). Higher circulating expression levels of miR-221 associated with poor overall survival in renal cell carcinoma patients. Tumour Biol. 35 4057–4066. 10.1007/s13277-013-1531-3 PubMed DOI

Trajkovic K., Hsu C., Chiantia S., Rajendran L., Wenzel D., Wieland F., et al. (2008). Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science 319 1244–1247. 10.1126/science.1153124 PubMed DOI

Tsui K. H., Shvarts O., Smith R. B., Figlin R., de Kernion J. B., Belldegrun A. (2000). Renal cell carcinoma: prognostic significance of incidentally detected tumors. J. Urol. 163 426–430. 10.1016/s0022-5347(05)67892-5 PubMed DOI

Tusong H., Maolakuerban N., Guan J., Rexiati M., Wang W. G., Azhati B., et al. (2017). Functional analysis of serum microRNAs miR-21 and miR-106a in renal cell carcinoma. Cancer Biomark. 18 79–85. 10.3233/cbm-160676 PubMed DOI

Tzimagiorgis G., Michailidou E. Z., Kritis A., Markopoulos A. K., Kouidou S. (2011). Recovering circulating extracellular or cell-free RNA from bodily fluids. Cancer Epidemiol. 35 580–589. 10.1016/j.canep.2011.02.016 PubMed DOI

Vasudev N. S., Wilson M., Stewart G. D., Adeyoju A., Cartledge J., Kimuli M., et al. (2020). Challenges of early renal cancer detection: symptom patterns and incidental diagnosis rate in a multicentre prospective UK cohort of patients presenting with suspected renal cancer. BMJ Open 10:e035938. 10.1136/bmjopen-2019-035938 PubMed DOI PMC

Vergho D., Kneitz S., Rosenwald A., Scherer C., Spahn M., Burger M., et al. (2014). Combination of expression levels of miR-21 and miR-126 is associated with cancer-specific survival in clear-cell renal cell carcinoma. BMC Cancer 14:25. 10.1186/1471-2407-14-25 PubMed DOI PMC

Victoria Martinez B., Dhahbi J. M., Nunez Lopez Y. O., Lamperska K., Golusinski P., Luczewski L., et al. (2015). Circulating small non-coding RNA signature in head and neck squamous cell carcinoma. Oncotarget 6 19246–19263. 10.18632/oncotarget.4266 PubMed DOI PMC

Villarroya-Beltri C., Gutiérrez-Vázquez C., Sánchez-Cabo F., Pérez-Hernández D., Vázquez J., Martin-Cofreces N., et al. (2013). Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs. Nat. Commun. 4:2980. PubMed PMC

Vojtech L., Woo S., Hughes S., Levy C., Ballweber L., Sauteraud R. P., et al. (2014). Exosomes in human semen carry a distinctive repertoire of small non-coding RNAs with potential regulatory functions. Nucleic Acids Res. 42 7290–7304. 10.1093/nar/gku347 PubMed DOI PMC

Wagner J., Riwanto M., Besler C., Knau A., Fichtlscherer S., Röxe T., et al. (2013). Characterization of levels and cellular transfer of circulating lipoprotein-bound microRNAs. Arterioscler Thromb Vasc. Biol. 33 1392–1400. 10.1161/atvbaha.112.300741 PubMed DOI

Wang C., Hu J., Lu M., Gu H., Zhou X., Chen X., et al. (2015). A panel of five serum miRNAs as a potential diagnostic tool for early-stage renal cell carcinoma. Sci. Rep. 5:7610. PubMed PMC

Wang C., Wu C., Yang Q., Ding M., Zhong J., Zhang C. Y., et al. (2016). miR-28-5p acts as a tumor suppressor in renal cell carcinoma for multiple antitumor effects by targeting RAP1B. Oncotarget 7 73888–73902. 10.18632/oncotarget.12516 PubMed DOI PMC

Wang K., Yuan Y., Cho J. H., McClarty S., Baxter D., Galas D. J. (2012). Comparing the MicroRNA spectrum between serum and plasma. PLoS One 7:e41561. 10.1371/journal.pone.0041561 PubMed DOI PMC

Wang L., Yang G., Zhao D., Wang J., Bai Y., Peng Q., et al. (2019). CD103-positive CSC exosome promotes EMT of clear cell renal cell carcinoma: role of remote MiR-19b-3p. Mol. Cancer 18:86. PubMed PMC

Wang Q., Wu G., Zhang Z., Tang Q., Zheng W., Chen X., et al. (2018). Long non-coding RNA HOTTIP promotes renal cell carcinoma progression through the regulation of the miR-615/IGF-2 pathway. Int. J. Oncol. 53 2278–2288. PubMed

Wang X., Wang T., Chen C., Wu Z., Bai P., Li S., et al. (2018). Serum exosomal miR-210 as a potential biomarker for clear cell renal cell carcinoma. J. Cell. Biochem. 120 1492–1502. 10.1002/jcb.27347 PubMed DOI

Weidle U. H., Birzele F., Kollmorgen G., Ruger R. (2017). Long non-coding RNAs and their role in metastasis. Cancer Genomics Proteomics 14 143–160. PubMed PMC

Westerman M. E., Shapiro D. D., Tannir N. M., Campbell M. T., Matin S. F., Karam J. A., et al. (2020). Survival following cytoreductive nephrectomy: a comparison of existing prognostic models. BJU Int. 10.1111/bju.15160 [Epub ahead of print]. PubMed DOI

Wu Y., Wang Y. Q., Weng W. W., Zhang Q. Y., Yang X. Q., Gan H. L., et al. (2016). A serum-circulating long noncoding RNA signature can discriminate between patients with clear cell renal cell carcinoma and healthy controls. Oncogenesis 5:e192. 10.1038/oncsis.2015.48 PubMed DOI PMC

Wu Z., Wang W., Wang Y., Wang X., Sun S., Yao Y., et al. (2020). Long noncoding RNA LINC00963 promotes breast cancer progression by functioning as a molecular sponge for microRNA-625 and thereby upregulating HMGA1. Cell Cycle 19 610–624. 10.1080/15384101.2020.1728024 PubMed DOI PMC

Wulfken L. M., Moritz R., Ohlmann C., Holdenrieder S., Jung V., Becker F., et al. (2011). MicroRNAs in renal cell carcinoma: diagnostic implications of serum miR-1233 levels. PLoS One 6:e25787. 10.1371/journal.pone.0025787 PubMed DOI PMC

Xiao W., Lou N., Ruan H., Bao L., Xiong Z., Yuan C., et al. (2017). Mir-144-3p promotes cell proliferation, metastasis, sunitinib resistance in clear cell Renal cell carcinoma by downregulating ARID1A. Cell Physiol. Biochem. 43 2420–2433. 10.1159/000484395 PubMed DOI

Xu Y., Tong Y., Zhu J., Lei Z., Wan L., Zhu X., et al. (2017). An increase in long non-coding RNA PANDAR is associated with poor prognosis in clear cell renal cell carcinoma. BMC Cancer 17:373. 10.1186/s12885-017-3339-9 PubMed DOI PMC

Yadav S., Khandelwal M., Seth A., Saini A. K., Dogra P. N., Sharma A. (2017). Serum microRNA expression profiling: potential diagnostic implications of a panel of serum microRNAs for clear cell renal cell cancer. Urology 104 64–69. 10.1016/j.urology.2017.03.013 PubMed DOI

Yang C., Cai W. C., Dong Z. T., Guo J. W., Zhao Y. J., Sui C. J., et al. (2019). lncARSR promotes liver cancer stem cells expansion via STAT3 pathway. Gene 687 73–81. 10.1016/j.gene.2018.10.087 PubMed DOI

Yang N., Kaur S., Volinia S., Greshock J., Lassus H., Hasegawa K., et al. (2008). MicroRNA microarray identifies Let-7i as a novel biomarker and therapeutic target in human epithelial ovarian cancer. Cancer Res. 68 10307–10314. 10.1158/0008-5472.can-08-1954 PubMed DOI PMC

Yang T., Zhou H., Liu P., Yan L., Yao W., Chen K., et al. (2017). lncRNA PVT1 and its splicing variant function as competing endogenous RNA to regulate clear cell renal cell carcinoma progression. Oncotarget 8 85353–85367. 10.18632/oncotarget.19743 PubMed DOI PMC

Yao N., Yu L., Zhu B., Gan H. Y., Guo B. Q. (2018). LncRNA GIHCG promotes development of ovarian cancer by regulating microRNA-429. Eur. Rev. Med. Pharmacol. Sci. 22 8127–8134. PubMed

Ye Z., Duan J., Wang L., Ji Y., Qiao B. (2019). LncRNA-LET inhibits cell growth of clear cell renal cell carcinoma by regulating miR-373-3p. Cancer Cell Int. 19:311. PubMed PMC

Yeri A., Courtright A., Reiman R., Carlson E., Beecroft T., Janss A., et al. (2017). Total extracellular small RNA profiles from plasma, saliva, and urine of healthy subjects. Sci. Rep. 7:44061. PubMed PMC

Yu G., Yao W., Gumireddy K., Li A., Wang J., Xiao W., et al. (2014). Pseudogene PTENP1 functions as a competing endogenous RNA to suppress clear-cell renal cell carcinoma progression. Mol. Cancer Ther. 13 3086–3097. 10.1158/1535-7163.mct-14-0245 PubMed DOI PMC

Zaman M. S., Shahryari V., Deng G., Thamminana S., Saini S., Majid S., et al. (2012). Up-regulation of microRNA-21 correlates with lower kidney cancer survival. PLoS One 7:e31060. 10.1371/journal.pone.0031060 PubMed DOI PMC

Zang C., Sun J., Liu W., Chu C., Jiang L., Ge R. (2019). miRNA-21 promotes cell proliferation and invasion via VHL/PI3K/AKT in papillary thyroid carcinoma. Hum. Cell 32 428–436. 10.1007/s13577-019-00254-4 PubMed DOI

Zaporozhchenko I. A., Ponomaryova A. A., Rykova E. Y., Laktionov P. P. (2018). The potential of circulating cell-free RNA as a cancer biomarker: challenges and opportunities. Expert Rev. Mol. Diagn. 18 133–145. 10.1080/14737159.2018.1425143 PubMed DOI

Zeng M., Zhu L., Li L., Kang C. (2017). miR-378 suppresses the proliferation, migration and invasion of colon cancer cells by inhibiting SDAD1. Cell Mol. Biol. Lett. 22:12. PubMed PMC

Zhai Q., Zhou L., Zhao C., Wan J., Yu Z., Guo X., et al. (2012). Identification of miR-508-3p and miR-509-3p that are associated with cell invasion and migration and involved in the apoptosis of renal cell carcinoma. Biochem. Biophys. Res. Commun. 419 621–626. 10.1016/j.bbrc.2012.02.060 PubMed DOI

Zhang A., Liu Y., Shen Y., Xu Y., Li X. (2011). miR-21 modulates cell apoptosis by targeting multiple genes in renal cell carcinoma. Urology 78 474.e13–474.e19. 10.1016/j.urology.2011.03.030 PubMed DOI

Zhang G. J., Zhou H., Xiao H. X., Li Y., Zhou T. (2014). MiR-378 is an independent prognostic factor and inhibits cell growth and invasion in colorectal cancer. BMC Cancer 14:109. 10.1186/1471-2407-14-109 PubMed DOI PMC

Zhang H. L., Yang L. F., Zhu Y., Yao X. D., Zhang S. L., Dai B., et al. (2011). Serum miRNA-21: elevated levels in patients with metastatic hormone-refractory prostate cancer and potential predictive factor for the efficacy of docetaxel-based chemotherapy. Prostate 71 326–331. 10.1002/pros.21246 PubMed DOI

Zhang L., Yu D. (2019). Exosomes in cancer development, metastasis, and immunity. Biochim. Biophys. Acta Rev. Cancer 1871 455–468. 10.1016/j.bbcan.2019.04.004 PubMed DOI PMC

Zhang W., Ni M., Su Y., Wang H., Zhu S., Zhao A., et al. (2018). MicroRNAs in serum exosomes as potential biomarkers in clear-cell renal cell carcinoma. Eur. Urol. Focus 4 412–419. 10.1016/j.euf.2016.09.007 PubMed DOI

Zhang W. B., Pan Z. Q., Yang Q. S., Zheng X. M. (2013). Tumor suppressive miR-509-5p contributes to cell migration, proliferation and antiapoptosis in renal cell carcinoma. Ir. J. Med. Sci. 182 621–627. 10.1007/s11845-013-0941-y PubMed DOI

Zhang X., Mao L., Li L., He Z., Wang N., Song Y. (2019). Long noncoding RNA GIHCG functions as an oncogene and serves as a serum diagnostic biomarker for cervical cancer. J. Cancer 10 672–681. 10.7150/jca.28525 PubMed DOI PMC

Zhao A., Li G., Peoc’h M., Genin C., Gigante M. (2013). Serum miR-210 as a novel biomarker for molecular diagnosis of clear cell renal cell carcinoma. Exp. Mol. Pathol. 94 115–120. 10.1016/j.yexmp.2012.10.005 PubMed DOI

Zhao L., Liu K., Pan X., Quan J., Zhou L., Li Z., et al. (2019a). miR-625-3p promotes migration and invasion and reduces apoptosis of clear cell renal cell carcinoma. Am. J. Transl. Res. 11 6475–6486. PubMed PMC

Zhao L., Quan J., Li Z., Pan X., Wang J., Xu J., et al. (2019b). MicroRNA-222-3p promotes tumor cell migration and invasion and inhibits apoptosis, and is correlated with an unfavorable prognosis of patients with renal cell carcinoma. Int. J. Mol. Med. 43 525–534. PubMed

Zhao Y. J., Song X., Niu L., Tang Y., Song X., Xie L. (2019). Circulating Exosomal miR-150-5p and miR-99b-5p as diagnostic biomarkers for colorectal cancer. Front. Oncol. 9:1129. 10.3389/fonc.2019.01129 PubMed DOI PMC

Zhou Y., van Melle M., Singh H., Hamilton W., Lyratzopoulos G., Walter F. M. (2019a). Quality of the diagnostic process in patients presenting with symptoms suggestive of bladder or kidney cancer: a systematic review. BMJ Open 9:e029143. 10.1136/bmjopen-2019-029143 PubMed DOI PMC

Zhou Y., Yin L., Li H., Liu L. H., Xiao T. (2019b). The LncRNA LINC00963 facilitates osteosarcoma proliferation and invasion by suppressing miR-204-3p/FN1 axis. Cancer Biol. Ther. 20 1141–1148. 10.1080/15384047.2019.1598766 PubMed DOI PMC

Zhu H., Wang S., Shen H., Zheng X., Xu X. (2020). SP1/AKT/FOXO3 signaling is involved in miR-362-3p-mediated inhibition of cell-cycle pathway and EMT progression in renal cell carcinoma. Front. Cell Dev. Biol. 8:297. 10.3389/fcell.2020.00297 PubMed DOI PMC

Znaor A., Lortet-Tieulent J., Laversanne M., Jemal A., Bray F. (2015). International variations and trends in renal cell carcinoma incidence and mortality. Eur. Urol. 67 519–530. 10.1016/j.eururo.2014.10.002 PubMed DOI

Zou S. L., Chen Y. L., Ge Z. Z., Qu Y. Y., Cao Y., Kang Z. X. (2019). Downregulation of serum exosomal miR-150-5p is associated with poor prognosis in patients with colorectal cancer. Cancer Biomark 26 69–77. 10.3233/cbm-190156 PubMed DOI

Zou X., Zhong J., Li J., Su Z., Chen Y., Deng W., et al. (2016). miR-362-3p targets nemo-like kinase and functions as a tumor suppressor in renal cancer cells. Mol. Med. Rep. 13 994–1002. 10.3892/mmr.2015.4632 PubMed DOI