Brain metastases are the most frequent intracranial tumors in adults and the cause of death in almost one-fourth of cases. The incidence of brain metastases is steadily increasing. The main reason for this increase could be the introduction of new and more efficient therapeutic strategies that lead to longer survival but, at the same time, cause a higher risk of brain parenchyma infiltration. In addition, the advances in imaging methodology, which provide earlier identification of brain metastases, may also be a reason for the higher recorded number of patients with these tumors. Metastasis is a complex biological process that is still largely unexplored, influenced by many factors and involving many molecules. A deeper understanding of the process will allow the discovery of more effective diagnostic and therapeutic approaches that could improve the quality and length of patient survival. Recent studies have shown that microRNAs (miRNAs) are essential molecules that are involved in specific steps of the metastatic cascade. MiRNAs are endogenously expressed small non-coding RNAs that act as post-transcriptional regulators of gene expression and thus regulate most cellular processes. The dysregulation of these molecules has been implicated in many cancers, including brain metastases. Therefore, miRNAs represent promising diagnostic molecules and therapeutic targets in brain metastases. This review summarizes the current knowledge on the importance of miRNAs in brain metastasis, focusing on their involvement in the metastatic cascade and their potential clinical implications.

Central European Institute of Technology Masaryk University 625 00 Brno Czech Republic

Department of Biology Faculty of Medicine Masaryk University 625 00 Brno Czech Republic

Department of Comprehensive Cancer Care Masaryk Memorial Cancer Institute and Faculty of Medicine of Masaryk University 656 53 Brno Czech Republic

Department of Neurosurgery St Annes University Hospital Brno and Faculty of Medicine of Masaryk University 656 91 Brno Czech Republic

Department of Neurosurgery University Hospital Brno and Faculty of Medicine of Masaryk University 625 00 Brno Czech Republic

Department of Pathology University Hospital Brno 625 00 Brno Czech Republic

Department of Radiation Oncology Masaryk Memorial Cancer Institute and Faculty of Medicine of Masaryk University 656 53 Brno Czech Republic

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Nayak L., Lee E.Q., Wen P.Y. Epidemiology of Brain Metastases. Curr. Oncol. Rep. 2012;14:48–54. doi: 10.1007/s11912-011-0203-y. PubMed DOI

Smedby K.E., Brandt L., Bäcklund M.L., Blomqvist P. Brain Metastases Admissions in Sweden between 1987 and 2006. Br. J. Cancer. 2009;101:1919–1924. doi: 10.1038/sj.bjc.6605373. PubMed DOI PMC

Niemiec M., Głogowski M., Tyc-Szczepaniak D., Wierzchowski M., Kępka L. Characteristics of Long-Term Survivors of Brain Metastases from Lung Cancer. Rep. Pract. Oncol. Radiother. 2011;16:49–53. doi: 10.1016/j.rpor.2011.01.002. PubMed DOI PMC

Watabe K. Non-Coding RNAs in Cancer Brain Metastasis. Front. Biosci. 2016;8:187–202. doi: 10.2741/s457. PubMed DOI PMC

Sperduto P.W., Kased N., Roberge D., Xu Z., Shanley R., Luo X., Sneed P.K., Chao S.T., Weil R.J., Suh J., et al. Summary Report on the Graded Prognostic Assessment: An Accurate and Facile Diagnosis-Specific Tool to Estimate Survival for Patients with Brain Metastases. J. Clin. Oncol. 2012;30:419–425. doi: 10.1200/JCO.2011.38.0527. PubMed DOI PMC

Barnholtz-Sloan J.S., Sloan A.E., Davis F.G., Vigneau F.D., Lai P., Sawaya R.E. Incidence Proportions of Brain Metastases in Patients Diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J. Clin. Oncol. 2004;22:2865–2872. doi: 10.1200/JCO.2004.12.149. PubMed DOI

Schouten L.J., Rutten J., Huveneers H.A.M., Twijnstra A. Incidence of Brain Metastases in a Cohort of Patients with Carcinoma of the Breast, Colon, Kidney, and Lung and Melanoma. Cancer. 2002;94:2698–2705. doi: 10.1002/cncr.10541. PubMed DOI

Ostrom Q.T., Wright C.H., Barnholtz-Sloan J.S. Handbook of Clinical Neurology. Volume 149. Elsevier; Amsterdam, The Netherlands: 2018. Brain Metastases: Epidemiology; pp. 27–42. PubMed

Cagney D.N., Martin A.M., Catalano P.J., Redig A.J., Lin N.U., Lee E.Q., Wen P.Y., Dunn I.F., Bi W.L., Weiss S.E., et al. Incidence and Prognosis of Patients with Brain Metastases at Diagnosis of Systemic Malignancy: A Population-Based Study. Neuro-Oncol. 2017;19:1511–1521. doi: 10.1093/neuonc/nox077. PubMed DOI PMC

Martin A.M., Cagney D.N., Catalano P.J., Warren L.E., Bellon J.R., Punglia R.S., Claus E.B., Lee E.Q., Wen P.Y., Haas-Kogan D.A., et al. Brain Metastases in Newly Diagnosed Breast Cancer: A Population-Based Study. JAMA Oncol. 2017;3:1069. doi: 10.1001/jamaoncol.2017.0001. PubMed DOI PMC

Ramakrishna N., Temin S., Chandarlapaty S., Crews J.R., Davidson N.E., Esteva F.J., Giordano S.H., Gonzalez-Angulo A.M., Kirshner J.J., Krop I., et al. Recommendations on Disease Management for Patients with Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases: American Society of Clinical Oncology Clinical Practice Guideline. J. Clin. Oncol. 2014;32:2100–2108. doi: 10.1200/JCO.2013.54.0955. PubMed DOI PMC

Langley R.R., Fidler I.J. The Seed and Soil Hypothesis Revisited-The Role of Tumor-Stroma Interactions in Metastasis to Different Organs. Int. J. Cancer. 2011;128:2527–2535. doi: 10.1002/ijc.26031. PubMed DOI PMC

Kuzet S.-E., Gaggioli C. Fibroblast Activation in Cancer: When Seed Fertilizes Soil. Cell Tissue Res. 2016;365:607–619. doi: 10.1007/s00441-016-2467-x. PubMed DOI

Kaplan R.N., Riba R.D., Zacharoulis S., Bramley A.H., Vincent L., Costa C., MacDonald D.D., Jin D.K., Shido K., Kerns S.A., et al. VEGFR1-Positive Haematopoietic Bone Marrow Progenitors Initiate the Pre-Metastatic Niche. Nature. 2005;438:820–827. doi: 10.1038/nature04186. PubMed DOI PMC

Zhang L., Zhang S., Yao J., Lowery F.J., Zhang Q., Huang W.-C., Li P., Li M., Wang X., Zhang C., et al. Microenvironment-Induced PTEN Loss by Exosomal MicroRNA Primes Brain Metastasis Outgrowth. Nature. 2015;527:100–104. doi: 10.1038/nature15376. PubMed DOI PMC

Draffin J.E., McFarlane S., Hill A., Johnston P.G., Waugh D.J.J. CD44 Potentiates the Adherence of Metastatic Prostate and Breast Cancer Cells to Bone Marrow Endothelial Cells. Cancer Res. 2004;64:5702–5711. doi: 10.1158/0008-5472.CAN-04-0389. PubMed DOI

Brabletz T. To Differentiate or Not—Routes towards Metastasis. Nat. Rev. Cancer. 2012;12:425–436. doi: 10.1038/nrc3265. PubMed DOI

Rettig M., Trinidad K., Pezeshkpour G., Frost P., Sharma S., Moatamed F., Tamanoi F., Mortazavi F. PAK1 Kinase Promotes Cell Motility and Invasiveness through CRK-II Serine Phosphorylation in Non-Small Cell Lung Cancer Cells. PLoS ONE. 2012;7:e42012. doi: 10.1371/journal.pone.0042012. PubMed DOI PMC

Craene B.D., Berx G. Regulatory Networks Defining EMT during Cancer Initiation and Progression. Nat. Rev. Cancer. 2013;13:97–110. doi: 10.1038/nrc3447. PubMed DOI

Mani S.A., Guo W., Liao M.-J., Eaton E.N., Ayyanan A., Zhou A.Y., Brooks M., Reinhard F., Zhang C.C., Shipitsin M., et al. The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells. Cell. 2008;133:704–715. doi: 10.1016/j.cell.2008.03.027. PubMed DOI PMC

Simpson C.D., Anyiwe K., Schimmer A.D. Anoikis Resistance and Tumor Metastasis. Cancer Lett. 2008;272:177–185. doi: 10.1016/j.canlet.2008.05.029. PubMed DOI

Luzzi K.J., MacDonald I.C., Schmidt E.E., Kerkvliet N., Morris V.L., Chambers A.F., Groom A.C. Multistep Nature of Metastatic Inefficiency. Am. J. Pathol. 1998;153:865–873. doi: 10.1016/S0002-9440(10)65628-3. PubMed DOI PMC

Thiery J.P., Acloque H., Huang R.Y.J., Nieto M.A. Epithelial-Mesenchymal Transitions in Development and Disease. Cell. 2009;139:871–890. doi: 10.1016/j.cell.2009.11.007. PubMed DOI

Wang Y., Bu F., Royer C., Serres S., Larkin J.R., Soto M.S., Sibson N.R., Salter V., Fritzsche F., Turnquist C., et al. ASPP2 Controls Epithelial Plasticity and Inhibits Metastasis through β-Catenin-Dependent Regulation of ZEB1. Nat. Cell Biol. 2014;16:1092–1104. doi: 10.1038/ncb3050. PubMed DOI

Díaz-López A., Díaz-Martín J., Moreno-Bueno G., Cuevas E.P., Santos V., Olmeda D., Portillo F., Palacios J., Cano A. Zeb1 and Snail1 Engage MiR-200f Transcriptional and Epigenetic Regulation during EMT: EMT Players Controlling Epithelial Plasticity. Int. J. Cancer. 2015;136:E62–E73. doi: 10.1002/ijc.29177. PubMed DOI

Sun T., Zhao N., Zhao X., Gu Q., Zhang S., Che N., Wang X., Du J., Liu Y., Sun B. Expression and Functional Significance of Twist1 in Hepatocellular Carcinoma: Its Role in Vasculogenic Mimicry. Hepatology. 2010;51:545–556. doi: 10.1002/hep.23311. PubMed DOI

Ocaña O.H., Córcoles R., Fabra Á., Moreno-Bueno G., Acloque H., Vega S., Barrallo-Gimeno A., Cano A., Nieto M.A. Metastatic Colonization Requires the Repression of the Epithelial-Mesenchymal Transition Inducer Prrx1. Cancer Cell. 2012;22:709–724. doi: 10.1016/j.ccr.2012.10.012. PubMed DOI

Wang J., He H., Jiang Q., Wang Y., Jia S. CBX6 Promotes HCC Metastasis Via Transcription Factors Snail/Zeb1-Mediated EMT Mechanism. Onco Targets Ther. 2020;13:12489–12500. doi: 10.2147/OTT.S257363. PubMed DOI PMC

Morrison C.D., Parvani J.G., Schiemann W.P. The Relevance of the TGF-β Paradox to EMT-MET Programs. Cancer Lett. 2013;341:30–40. doi: 10.1016/j.canlet.2013.02.048. PubMed DOI PMC

Tan E.-J., Olsson A.-K., Moustakas A. Reprogramming during Epithelial to Mesenchymal Transition under the Control of TGFβ. Cell Adhes. Migr. 2015;9:233–246. doi: 10.4161/19336918.2014.983794. PubMed DOI PMC

VanderVorst K., Dreyer C.A., Konopelski S.E., Lee H., Ho H.-Y.H., Carraway K.L. Wnt/PCP Signaling Contribution to Carcinoma Collective Cell Migration and Metastasis. Cancer Res. 2019;79:1719–1729. doi: 10.1158/0008-5472.CAN-18-2757. PubMed DOI PMC

Li L., Tang P., Li S., Qin X., Yang H., Wu C., Liu Y. Notch Signaling Pathway Networks in Cancer Metastasis: A New Target for Cancer Therapy. Med. Oncol. 2017;34:180. doi: 10.1007/s12032-017-1039-6. PubMed DOI

Joseph J.P., Harishankar M.K., Pillai A.A., Devi A. Hypoxia Induced EMT: A Review on the Mechanism of Tumor Progression and Metastasis in OSCC. Oral Oncol. 2018;80:23–32. doi: 10.1016/j.oraloncology.2018.03.004. PubMed DOI

Brizel D.M., Schroeder T., Scher R.L., Walenta S., Clough R.W., Dewhirst M.W., Mueller-Klieser W. Elevated Tumor Lactate Concentrations Predict for an Increased Risk of Metastases in Head-and-Neck Cancer. Int. J. Radiat. Oncol. 2001;51:349–353. doi: 10.1016/S0360-3016(01)01630-3. PubMed DOI

Goetze K. Lactate Enhances Motility of Tumor Cells and Inhibits Monocyte Migration and Cytokine Release. Int. J. Oncol. 2011;39:453–463. doi: 10.3892/ijo.2011.1055. PubMed DOI

Knudsen E.S., Ertel A., Davicioni E., Kline J., Schwartz G.F., Witkiewicz A.K. Progression of Ductal Carcinoma in Situ to Invasive Breast Cancer Is Associated with Gene Expression Programs of EMT and Myoepithelia. Breast Cancer Res. Treat. 2012;133:1009–1024. doi: 10.1007/s10549-011-1894-3. PubMed DOI

Thiery J.P. Epithelial–Mesenchymal Transitions in Tumour Progression. Nat. Rev. Cancer. 2002;2:442–454. doi: 10.1038/nrc822. PubMed DOI

Wang Y., Zhou B.P. Epithelial-Mesenchymal Transition in Breast Cancer Progression and Metastasis. Chin. J. Cancer. 2011;30:603–611. doi: 10.5732/cjc.011.10226. PubMed DOI PMC

Roh M.R., Zheng Z., Kim H.S., Kwon J.E., Jeung H.-C., Rha S.Y., Chung K.Y. Differential Expression Patterns of MMPs and Their Role in the Invasion of Epithelial Premalignant Tumors and Invasive Cutaneous Squamous Cell Carcinoma. Exp. Mol. Pathol. 2012;92:236–242. doi: 10.1016/j.yexmp.2012.01.003. PubMed DOI

Rahman M., Mohammed S. Breast Cancer Metastasis and the Lymphatic System. Oncol. Lett. 2015;10:1233–1239. doi: 10.3892/ol.2015.3486. PubMed DOI PMC

Wong A.D., Searson P.C. Live-Cell Imaging of Invasion and Intravasation in an Artificial Microvessel Platform. Cancer Res. 2014;74:4937–4945. doi: 10.1158/0008-5472.CAN-14-1042. PubMed DOI PMC

Bolós V., Mira E., Martínez-Poveda B., Luxán G., Cañamero M., Martínez-A C., Mañes S., de la Pompa J.L. Notch Activation Stimulates Migration of Breast Cancer Cells and Promotes Tumor Growth. Breast Cancer Res. 2013;15:R54. doi: 10.1186/bcr3447. PubMed DOI PMC

Sonoshita M., Aoki M., Fuwa H., Aoki K., Hosogi H., Sakai Y., Hashida H., Takabayashi A., Sasaki M., Robine S., et al. Suppression of Colon Cancer Metastasis by Aes through Inhibition of Notch Signaling. Cancer Cell. 2011;19:125–137. doi: 10.1016/j.ccr.2010.11.008. PubMed DOI

Khuon S., Liang L., Dettman R.W., Sporn P.H.S., Wysolmerski R.B., Chew T.-L. Myosin Light Chain Kinase Mediates Transcellular Intravasation of Breast Cancer Cells through the Underlying Endothelial Cells: A Three-Dimensional FRET Study. J. Cell Sci. 2010;123:431–440. doi: 10.1242/jcs.053793. PubMed DOI PMC

Arvanitis C., Khuon S., Spann R., Ridge K.M., Chew T.-L. Structure and Biomechanics of the Endothelial Transcellular Circumferential Invasion Array in Tumor Invasion. PLoS ONE. 2014;9:e89758. doi: 10.1371/journal.pone.0089758. PubMed DOI PMC

Labelle M., Hynes R.O. The Initial Hours of Metastasis: The Importance of Cooperative Host–Tumor Cell Interactions during Hematogenous Dissemination. Cancer Discov. 2012;2:1091–1099. doi: 10.1158/2159-8290.CD-12-0329. PubMed DOI PMC

Mamessier E., Sylvain A., Thibult M.-L., Houvenaeghel G., Jacquemier J., Castellano R., Gonçalves A., André P., Romagné F., Thibault G., et al. Human Breast Cancer Cells Enhance Self Tolerance by Promoting Evasion from NK Cell Antitumor Immunity. J. Clin. Investig. 2011;121:3609–3622. doi: 10.1172/JCI45816. PubMed DOI PMC

Moose D.L., Krog B.L., Kim T.-H., Zhao L., Williams-Perez S., Burke G., Rhodes L., Vanneste M., Breheny P., Milhem M., et al. Cancer Cells Resist Mechanical Destruction in Circulation via RhoA/Actomyosin-Dependent Mechano-Adaptation. Cell Rep. 2020;30:3864–3874.e6. doi: 10.1016/j.celrep.2020.02.080. PubMed DOI PMC

Kopp H.-G., Placke T., Salih H.R. Platelet-Derived Transforming Growth Factor-β Down-Regulates NKG2D Thereby Inhibiting Natural Killer Cell Antitumor Reactivity. Cancer Res. 2009;69:7775–7783. doi: 10.1158/0008-5472.CAN-09-2123. PubMed DOI

Kienast Y., von Baumgarten L., Fuhrmann M., Klinkert W.E.F., Goldbrunner R., Herms J., Winkler F. Real-Time Imaging Reveals the Single Steps of Brain Metastasis Formation. Nat. Med. 2010;16:116–122. doi: 10.1038/nm.2072. PubMed DOI

Valiente M., Obenauf A.C., Jin X., Chen Q., Zhang X.H.-F., Lee D.J., Chaft J.E., Kris M.G., Huse J.T., Brogi E., et al. Serpins Promote Cancer Cell Survival and Vascular Co-Option in Brain Metastasis. Cell. 2014;156:1002–1016. doi: 10.1016/j.cell.2014.01.040. PubMed DOI PMC

Liu Y., Kosaka A., Ikeura M., Kohanbash G., Fellows-Mayle W., Snyder L.A., Okada H. Premetastatic Soil and Prevention of Breast Cancer Brain Metastasis. Neuro-Oncol. 2013;15:891–903. doi: 10.1093/neuonc/not031. PubMed DOI PMC

Hanibuchi M., Kim S.-J., Fidler I.J., Nishioka Y. The Molecular Biology of Lung Cancer Brain Metastasis: An Overview of Current Comprehensions and Future Perspectives. J. Med. Investig. 2014;61:241–253. doi: 10.2152/jmi.61.241. PubMed DOI

Soto M.S., Serres S., Anthony D.C., Sibson N.R. Functional Role of Endothelial Adhesion Molecules in the Early Stages of Brain Metastasis. Neuro-Oncol. 2014;16:540–551. doi: 10.1093/neuonc/not222. PubMed DOI PMC

Wu K., Fukuda K., Xing F., Zhang Y., Sharma S., Liu Y., Chan M.D., Zhou X., Qasem S.A., Pochampally R., et al. Roles of the Cyclooxygenase 2 Matrix Metalloproteinase 1 Pathway in Brain Metastasis of Breast Cancer. J. Biol. Chem. 2015;290:9842–9854. doi: 10.1074/jbc.M114.602185. PubMed DOI PMC

Gunasinghe N.P.A.D., Wells A., Thompson E.W., Hugo H.J. Mesenchymal–Epithelial Transition (MET) as a Mechanism for Metastatic Colonisation in Breast Cancer. Cancer Metastasis Rev. 2012;31:469–478. doi: 10.1007/s10555-012-9377-5. PubMed DOI

Yoshida T., Ozawa Y., Kimura T., Sato Y., Kuznetsov G., Xu S., Uesugi M., Agoulnik S., Taylor N., Funahashi Y., et al. Eribulin Mesilate Suppresses Experimental Metastasis of Breast Cancer Cells by Reversing Phenotype from Epithelial–Mesenchymal Transition (EMT) to Mesenchymal–Epithelial Transition (MET) States. Br. J. Cancer. 2014;110:1497–1505. doi: 10.1038/bjc.2014.80. PubMed DOI PMC

Chao Y., Wu Q., Acquafondata M., Dhir R., Wells A. Partial Mesenchymal to Epithelial Reverting Transition in Breast and Prostate Cancer Metastases. Cancer Microenviron. 2012;5:19–28. doi: 10.1007/s12307-011-0085-4. PubMed DOI PMC

Wanner I.B., Anderson M.A., Song B., Levine J., Fernandez A., Gray-Thompson Z., Ao Y., Sofroniew M.V. Glial Scar Borders Are Formed by Newly Proliferated, Elongated Astrocytes That Interact to Corral Inflammatory and Fibrotic Cells via STAT3-Dependent Mechanisms after Spinal Cord Injury. J. Neurosci. 2013;33:12870–12886. doi: 10.1523/JNEUROSCI.2121-13.2013. PubMed DOI PMC

Lorger M., Felding-Habermann B. Capturing Changes in the Brain Microenvironment during Initial Steps of Breast Cancer Brain Metastasis. Am. J. Pathol. 2010;176:2958–2971. doi: 10.2353/ajpath.2010.090838. PubMed DOI PMC

Fitzgerald D.P., Palmieri D., Hua E., Hargrave E., Herring J.M., Qian Y., Vega-Valle E., Weil R.J., Stark A.M., Vortmeyer A.O., et al. Reactive Glia Are Recruited by Highly Proliferative Brain Metastases of Breast Cancer and Promote Tumor Cell Colonization. Clin. Exp. Metastasis. 2008;25:799–810. doi: 10.1007/s10585-008-9193-z. PubMed DOI PMC

Xing F., Kobayashi A., Okuda H., Watabe M., Pai S.K., Pandey P.R., Hirota S., Wilber A., Mo Y., Moore B.E., et al. Reactive Astrocytes Promote the Metastatic Growth of Breast Cancer Stem-like Cells by Activating Notch Signalling in Brain. EMBO Mol. Med. 2013;5:384–396. doi: 10.1002/emmm.201201623. PubMed DOI PMC

Ye X., Xu S., Xin Y., Yu S., Ping Y., Chen L., Xiao H., Wang B., Yi L., Wang Q., et al. Tumor-Associated Microglia/Macrophages Enhance the Invasion of Glioma Stem-like Cells via TGF-Β1 Signaling Pathway. J. Immunol. 2012;189:444–453. doi: 10.4049/jimmunol.1103248. PubMed DOI

Demeule M., Bertrand Y., Michaud-Levesque J., Jodoin J., Rolland Y., Gabathuler R., Béliveau R. Regulation of Plasminogen Activation: A Role for Melanotransferrin (P97) in Cell Migration. Blood. 2003;102:1723–1731. doi: 10.1182/blood-2003-01-0166. PubMed DOI

Dunn L.L., Sekyere E.O., Suryo Rahmanto Y., Richardson D.R. The Function of Melanotransferrin: A Role in Melanoma Cell Proliferation and Tumorigenesis. Carcinogenesis. 2006;27:2157–2169. doi: 10.1093/carcin/bgl045. PubMed DOI

Kim S.W., Choi H.J., Lee H.-J., He J., Wu Q., Langley R.R., Fidler I.J., Kim S.-J. Role of the Endothelin Axis in Astrocyte- and Endothelial Cell-Mediated Chemoprotection of Cancer Cells. Neuro-Oncol. 2014;16:1585–1598. doi: 10.1093/neuonc/nou128. PubMed DOI PMC

Chen Q., Boire A., Jin X., Valiente M., Er E.E., Lopez-Soto A., Jacob L.S., Patwa R., Shah H., Xu K., et al. Carcinoma–Astrocyte Gap Junctions Promote Brain Metastasis by CGAMP Transfer. Nature. 2016;533:493–498. doi: 10.1038/nature18268. PubMed DOI PMC

Neman J., Termini J., Wilczynski S., Vaidehi N., Choy C., Kowolik C.M., Li H., Hambrecht A.C., Roberts E., Jandial R. Human Breast Cancer Metastases to the Brain Display GABAergic Properties in the Neural Niche. Proc. Natl. Acad. Sci. USA. 2014;111:984–989. doi: 10.1073/pnas.1322098111. PubMed DOI PMC

Grupenmacher A.T., Halpern A.L., Bonaldo M.d.F., Huang C.-C., Hamm C.A., de Andrade A., Tomita T., Sredni S.T. Study of the Gene Expression and MicroRNA Expression Profiles of Malignant Rhabdoid Tumors Originated in the Brain (AT/RT) and in the Kidney (RTK) Childs Nerv. Syst. 2013;29:1977–1983. doi: 10.1007/s00381-013-2268-4. PubMed DOI

Huarte M., Rinn J.L. Large Non-Coding RNAs: Missing Links in Cancer? Hum. Mol. Genet. 2010;19:R152–R161. doi: 10.1093/hmg/ddq353. PubMed DOI PMC

International Human Genome Sequencing Consortium Initial Sequencing and Analysis of the Human Genome. Nature. 2001;409:860–921. doi: 10.1038/35057062. PubMed DOI

Lu J., Getz G., Miska E.A., Alvarez-Saavedra E., Lamb J., Peck D., Sweet-Cordero A., Ebert B.L., Mak R.H., Ferrando A.A., et al. MicroRNA Expression Profiles Classify Human Cancers. Nature. 2005;435:834–838. doi: 10.1038/nature03702. PubMed DOI

Volinia S., Calin G.A., Liu C.-G., Ambs S., Cimmino A., Petrocca F., Visone R., Iorio M., Roldo C., Ferracin M., et al. A MicroRNA Expression Signature of Human Solid Tumors Defines Cancer Gene Targets. Proc. Natl. Acad. Sci. USA. 2006;103:2257–2261. doi: 10.1073/pnas.0510565103. PubMed DOI PMC

MacRae I.J., Zhou K., Li F., Repic A., Brooks A.N., Cande W.Z., Adams P.D., Doudna J.A. Structural Basis for Double-Stranded RNA Processing by Dicer. Science. 2006;311:195–198. doi: 10.1126/science.1121638. PubMed DOI

Kobayashi H., Tomari Y. RISC Assembly: Coordination between Small RNAs and Argonaute Proteins. Biochim. Biophys. Acta BBA Gene Regul. Mech. 2016;1859:71–81. doi: 10.1016/j.bbagrm.2015.08.007. PubMed DOI

Chendrimada T.P., Gregory R.I., Kumaraswamy E., Norman J., Cooch N., Nishikura K., Shiekhattar R. TRBP Recruits the Dicer Complex to Ago2 for MicroRNA Processing and Gene Silencing. Nature. 2005;436:740–744. doi: 10.1038/nature03868. PubMed DOI PMC

Meister G., Tuschl T. Mechanisms of Gene Silencing by Double-Stranded RNA. Nature. 2004;431:343–349. doi: 10.1038/nature02873. PubMed DOI

Eichhorn S.W., Guo H., McGeary S.E., Rodriguez-Mias R.A., Shin C., Baek D., Hsu S., Ghoshal K., Villén J., Bartel D.P. MRNA Destabilization Is the Dominant Effect of Mammalian MicroRNAs by the Time Substantial Repression Ensues. Mol. Cell. 2014;56:104–115. doi: 10.1016/j.molcel.2014.08.028. PubMed DOI PMC

Lewis B.P., Shih I., Jones-Rhoades M.W., Bartel D.P., Burge C.B. Prediction of Mammalian MicroRNA Targets. Cell. 2003;115:787–798. doi: 10.1016/S0092-8674(03)01018-3. PubMed DOI

Tay Y., Zhang J., Thomson A.M., Lim B., Rigoutsos I. MicroRNAs to Nanog, Oct4 and Sox2 Coding Regions Modulate Embryonic Stem Cell Differentiation. Nature. 2008;455:1124–1128. doi: 10.1038/nature07299. PubMed DOI

Miska E.A., Alvarez-Saavedra E., Abbott A.L., Lau N.C., Hellman A.B., McGonagle S.M., Bartel D.P., Ambros V.R., Horvitz H.R. Most Caenorhabditis Elegans MicroRNAs Are Individually Not Essential for Development or Viability. PLoS Genet. 2007;3:e215. doi: 10.1371/journal.pgen.0030215. PubMed DOI PMC

Bernstein E., Kim S.Y., Carmell M.A., Murchison E.P., Alcorn H., Li M.Z., Mills A.A., Elledge S.J., Anderson K.V., Hannon G.J. Dicer Is Essential for Mouse Development. Nat. Genet. 2003;35:215–217. doi: 10.1038/ng1253. PubMed DOI

Vidigal J.A., Ventura A. The Biological Functions of MiRNAs: Lessons from in Vivo Studies. Trends Cell Biol. 2015;25:137–147. doi: 10.1016/j.tcb.2014.11.004. PubMed DOI PMC

Wang D., Zhang Z., O’Loughlin E., Wang L., Fan X., Lai E.C., Yi R. MicroRNA-205 Controls Neonatal Expansion of Skin Stem Cells by Modulating the PI(3)K Pathway. Nat. Cell Biol. 2013;15:1153–1163. doi: 10.1038/ncb2827. PubMed DOI PMC

Ventura A., Young A.G., Winslow M.M., Lintault L., Meissner A., Erkeland S.J., Newman J., Bronson R.T., Crowley D., Stone J.R., et al. Targeted Deletion Reveals Essential and Overlapping Functions of the MiR-17∼92 Family of MiRNA Clusters. Cell. 2008;132:875–886. doi: 10.1016/j.cell.2008.02.019. PubMed DOI PMC

Calin G.A., Sevignani C., Dumitru C.D., Hyslop T., Noch E., Yendamuri S., Shimizu M., Rattan S., Bullrich F., Negrini M., et al. Human MicroRNA Genes Are Frequently Located at Fragile Sites and Genomic Regions Involved in Cancers. Proc. Natl. Acad. Sci. USA. 2004;101:2999–3004. doi: 10.1073/pnas.0307323101. PubMed DOI PMC

Wan L., Pantel K., Kang Y. Tumor Metastasis: Moving New Biological Insights into the Clinic. Nat. Med. 2013;19:1450–1464. doi: 10.1038/nm.3391. PubMed DOI

Sun Y., Ma L. The Emerging Molecular Machinery and Therapeutic Targets of Metastasis. Trends Pharmacol. Sci. 2015;36:349–359. doi: 10.1016/j.tips.2015.04.001. PubMed DOI PMC

Kanchan R.K., Siddiqui J.A., Mahapatra S., Batra S.K., Nasser M.W. MicroRNAs Orchestrate Pathophysiology of Breast Cancer Brain Metastasis: Advances in Therapy. Mol. Cancer. 2020;19:29. doi: 10.1186/s12943-020-1140-x. PubMed DOI PMC

Ma L. Role of MiR-10b in Breast Cancer Metastasis. Breast Cancer Res. 2010;12:210. doi: 10.1186/bcr2720. PubMed DOI PMC

Burk U., Schubert J., Wellner U., Schmalhofer O., Vincan E., Spaderna S., Brabletz T. A Reciprocal Repression between ZEB1 and Members of the MiR-200 Family Promotes EMT and Invasion in Cancer Cells. EMBO Rep. 2008;9:582–589. doi: 10.1038/embor.2008.74. PubMed DOI PMC

Brabletz S., Brabletz T. The ZEB/MiR-200 Feedback Loop—A Motor of Cellular Plasticity in Development and Cancer? EMBO Rep. 2010;11:670–677. doi: 10.1038/embor.2010.117. PubMed DOI PMC

Kundu S.T., Byers L.A., Peng D.H., Roybal J.D., Diao L., Wang J., Tong P., Creighton C.J., Gibbons D.L. The MiR-200 Family and the MiR-183~96~182 Cluster Target Foxf2 to Inhibit Invasion and Metastasis in Lung Cancers. Oncogene. 2016;35:173–186. doi: 10.1038/onc.2015.71. PubMed DOI PMC

Ding X., Park S.I., McCauley L.K., Wang C.-Y. Signaling between Transforming Growth Factor β (TGF-β) and Transcription Factor SNAI2 Represses Expression of MicroRNA MiR-203 to Promote Epithelial-Mesenchymal Transition and Tumor Metastasis. J. Biol. Chem. 2013;288:10241–10253. doi: 10.1074/jbc.M112.443655. PubMed DOI PMC

Yu S.-J., Hu J.-Y., Kuang X.-Y., Luo J.-M., Hou Y.-F., Di G.-H., Wu J., Shen Z.-Z., Song H.-Y., Shao Z.-M. MicroRNA-200a Promotes Anoikis Resistance and Metastasis by Targeting YAP1 in Human Breast Cancer. Clin. Cancer Res. 2013;19:1389–1399. doi: 10.1158/1078-0432.CCR-12-1959. PubMed DOI

Mansoori B., Mohammadi A., Ghasabi M., Shirjang S., Dehghan R., Montazeri V., Holmskov U., Kazemi T., Duijf P., Gjerstorff M., et al. MiR-142-3p as Tumor Suppressor MiRNA in the Regulation of Tumorigenicity, Invasion and Migration of Human Breast Cancer by Targeting Bach-1 Expression. J. Cell. Physiol. 2019;234:9816–9825. doi: 10.1002/jcp.27670. PubMed DOI

Li H., Rokavec M., Jiang L., Horst D., Hermeking H. Antagonistic Effects of P53 and HIF1A on MicroRNA-34a Regulation of PPP1R11 and STAT3 and Hypoxia-Induced Epithelial to Mesenchymal Transition in Colorectal Cancer Cells. Gastroenterology. 2017;153:505–520. doi: 10.1053/j.gastro.2017.04.017. PubMed DOI

Pencheva N., Tran H., Buss C., Huh D., Drobnjak M., Busam K., Tavazoie S.F. Convergent Multi-MiRNA Targeting of ApoE Drives LRP1/LRP8-Dependent Melanoma Metastasis and Angiogenesis. Cell. 2012;151:1068–1082. doi: 10.1016/j.cell.2012.10.028. PubMed DOI PMC

Wang S., Li W., Wen C., Diao Y., Zhao T. MicroRNA-214 Promotes the EMT Process in Melanoma by Downregulating CADM1 Expression. Mol. Med. Rep. 2020;22:3795–3803. doi: 10.3892/mmr.2020.11446. PubMed DOI PMC

Penna E., Orso F., Cimino D., Tenaglia E., Lembo A., Quaglino E., Poliseno L., Haimovic A., Osella-Abate S., De Pittà C., et al. MicroRNA-214 Contributes to Melanoma Tumour Progression through Suppression of TFAP2C: MiR-214 and Melanoma Progression. EMBO J. 2011;30:1990–2007. doi: 10.1038/emboj.2011.102. PubMed DOI PMC

Cantini L., Bertoli G., Cava C., Dubois T., Zinovyev A., Caselle M., Castiglioni I., Barillot E., Martignetti L. Identification of MicroRNA Clusters Cooperatively Acting on Epithelial to Mesenchymal Transition in Triple Negative Breast Cancer. Nucleic Acids Res. 2019;47:2205–2215. doi: 10.1093/nar/gkz016. PubMed DOI PMC

Lv Z.-D., Yang D.-X., Liu X.-P., Jin L.-Y., Wang X.-G., Yang Z.-C., Liu D., Zhao J.-J., Kong B., Li F.-N., et al. MiR-212-5p Suppresses the Epithelial-Mesenchymal Transition in Triple-Negative Breast Cancer by Targeting Prrx2. Cell. Physiol. Biochem. 2017;44:1785–1795. doi: 10.1159/000485785. PubMed DOI

Zhao L., Zhao Y., He Y., Mao Y. MiR-19b Promotes Breast Cancer Metastasis through Targeting MYLIP and Its Related Cell Adhesion Molecules. Oncotarget. 2017;8:64330–64343. doi: 10.18632/oncotarget.19278. PubMed DOI PMC

Zhang L., Sullivan P.S., Goodman J.C., Gunaratne P.H., Marchetti D. MicroRNA-1258 Suppresses Breast Cancer Brain Metastasis by Targeting Heparanase. Cancer Res. 2011;71:645–654. doi: 10.1158/0008-5472.CAN-10-1910. PubMed DOI PMC

Zhang L., Dong Y., Zhu N., Tsoi H., Zhao Z., Wu C.W., Wang K., Zheng S., Ng S.S., Chan F.K., et al. MicroRNA-139-5p Exerts Tumor Suppressor Function by Targeting NOTCH1 in Colorectal Cancer. Mol. Cancer. 2014;13:124. doi: 10.1186/1476-4598-13-124. PubMed DOI PMC

Fan L., Wu Y., Wang J., He J., Han X. Sevoflurane Inhibits the Migration and Invasion of Colorectal Cancer Cells through Regulating ERK/MMP-9 Pathway by up-Regulating MiR-203. Eur. J. Pharmacol. 2019;850:43–52. doi: 10.1016/j.ejphar.2019.01.025. PubMed DOI

Cai H., Chen X., Tang Y., Deng Y. MicroRNA-194 Modulates Epithelial–Mesenchymal Transition in Human Colorectal Cancer Metastasis. Onco Targets Ther. 2017;10:1269–1278. doi: 10.2147/OTT.S125172. PubMed DOI PMC

Martello G., Rosato A., Ferrari F., Manfrin A., Cordenonsi M., Dupont S., Enzo E., Guzzardo V., Rondina M., Spruce T., et al. A MicroRNA Targeting Dicer for Metastasis Control. Cell. 2010;141:1195–1207. doi: 10.1016/j.cell.2010.05.017. PubMed DOI

Shao Y., Chen T., Zheng X., Yang S., Xu K., Chen X., Xu F., Wang L., Shen Y., Wang T., et al. Colorectal Cancer-Derived Small Extracellular Vesicles Establish an Inflammatory Premetastatic Niche in Liver Metastasis. Carcinogenesis. 2018;39:1368–1379. doi: 10.1093/carcin/bgy115. PubMed DOI

Wang D., Wang X., Si M., Yang J., Sun S., Wu H., Cui S., Qu X., Yu X. Exosome-Encapsulated MiRNAs Contribute to CXCL12/CXCR4-Induced Liver Metastasis of Colorectal Cancer by Enhancing M2 Polarization of Macrophages. Cancer Lett. 2020;474:36–52. doi: 10.1016/j.canlet.2020.01.005. PubMed DOI

Yang M., Chen J., Su F., Yu B., Su F., Lin L., Liu Y., Huang J.-D., Song E. Microvesicles Secreted by Macrophages Shuttle Invasion-Potentiating MicroRNAs into Breast Cancer Cells. Mol. Cancer. 2011;10:117. doi: 10.1186/1476-4598-10-117. PubMed DOI PMC

Zhou W., Fong M.Y., Min Y., Somlo G., Liu L., Palomares M.R., Yu Y., Chow A., O’Connor S.T.F., Chin A.R., et al. Cancer-Secreted MiR-105 Destroys Vascular Endothelial Barriers to Promote Metastasis. Cancer Cell. 2014;25:501–515. doi: 10.1016/j.ccr.2014.03.007. PubMed DOI PMC

Siegel R., Ward E., Brawley O., Jemal A. Cancer Statistics, 2011: The Impact of Eliminating Socioeconomic and Racial Disparities on Premature Cancer Deaths. CA. Cancer J. Clin. 2011;61:212–236. doi: 10.3322/caac.20121. PubMed DOI

Siegel R.L., Miller K.D., Jemal A. Cancer Statistics, 2016: Cancer Statistics, 2016. CA. Cancer J. Clin. 2016;66:7–30. doi: 10.3322/caac.21332. PubMed DOI

Mujoomdar A., Austin J.H.M., Malhotra R., Powell C.A., Pearson G.D.N., Shiau M.C., Raftopoulos H. Clinical Predictors of Metastatic Disease to the Brain from Non–Small Cell Lung Carcinoma: Primary Tumor Size, Cell Type, and Lymph Node Metastases. Radiology. 2007;242:882–888. doi: 10.1148/radiol.2423051707. PubMed DOI

Budczies J., von Winterfeld M., Klauschen F., Bockmayr M., Lennerz J.K., Denkert C., Wolf T., Warth A., Dietel M., Anagnostopoulos I., et al. The Landscape of Metastatic Progression Patterns across Major Human Cancers. Oncotarget. 2015;6:570–583. doi: 10.18632/oncotarget.2677. PubMed DOI PMC

Sørensen J.B., Hansen H.H., Hansen M., Dombernowsky P. Brain Metastases in Adenocarcinoma of the Lung: Frequency, Risk Groups, and Prognosis. J. Clin. Oncol. 1988;6:1474–1480. doi: 10.1200/JCO.1988.6.9.1474. PubMed DOI

Zhu Z., Li Q., Xu M., Qi Z. Effect of Whole-Brain and Intensity-Modulated Radiotherapy on Serum Levels of MiR-21 and Prognosis for Lung Cancer Metastatic to the Brain. Med. Sci. Monit. 2020;26:e924640. doi: 10.12659/MSM.924640. PubMed DOI PMC

Dong J., Zhang Z., Gu T., Xu S.-F., Dong L.-X., Li X., Fu B.-H., Fu Z.-Z. The Role of MicroRNA-21 in Predicting Brain Metastases from Non-Small Cell Lung Cancer. Onco Targets Ther. 2016;10:185–194. doi: 10.2147/OTT.S116619. PubMed DOI PMC

Singh M., Garg N., Venugopal C., Hallett R., Tokar T., McFarlane N., Mahendram S., Bakhshinyan D., Manoranjan B., Vora P., et al. STAT3 Pathway Regulates Lung-Derived Brain Metastasis Initiating Cell Capacity through MiR-21 Activation. Oncotarget. 2015;6:27461–27477. doi: 10.18632/oncotarget.4742. PubMed DOI PMC

Subramani A., Alsidawi S., Jagannathan S., Sumita K., Sasaki A.T., Aronow B., Warnick R.E., Lawler S., Driscoll J.J. The Brain Microenvironment Negatively Regulates MiRNA-768-3p to Promote K-Ras Expression and Lung Cancer Metastasis. Sci. Rep. 2013;3:2392. doi: 10.1038/srep02392. PubMed DOI PMC

Choi K.H., Shin C.H., Lee W.J., Ji H., Kim H.H. Dual-Strand Tumor Suppressor MiR-193b-3p and -5p Inhibit Malignant Phenotypes of Lung Cancer by Suppressing Their Common Targets. Biosci. Rep. 2019;39:BSR20190634. doi: 10.1042/BSR20190634. PubMed DOI PMC

Jiang C., Zhao H., Yang B., Sun Z., Li X., Hu X. Lnc-REG3G-3-1/MiR-215-3p Promotes Brain Metastasis of Lung Adenocarcinoma by Regulating Leptin and SLC2A5. Front. Oncol. 2020;10:1344. doi: 10.3389/fonc.2020.01344. PubMed DOI PMC

Jiang W., Hou L., Wei J., Du Y., Zhao Y., Deng X., Lin X. Hsa-MiR-217 Inhibits the Proliferation, Migration, and Invasion in Non-Small Cell Lung Cancer Cells Via Targeting SIRT1 and P53/KAI1 Signaling. Balk. Med. J. 2021;37:208–214. doi: 10.4274/balkanmedj.galenos.2020.2019.9.91. PubMed DOI PMC

Donzelli S., Mori F., Bellissimo T., Sacconi A., Casini B., Frixa T., Roscilli G., Aurisicchio L., Facciolo F., Pompili A., et al. Epigenetic Silencing of MiR-145-5p Contributes to Brain Metastasis. Oncotarget. 2015;6:35183–35201. doi: 10.18632/oncotarget.5930. PubMed DOI PMC

Zhao C., Xu Y., Zhang Y., Tan W., Xue J., Yang Z., Zhang Y., Lu Y., Hu X. Downregulation of MiR-145 Contributes to Lung Adenocarcinoma Cell Growth to Form Brain Metastases. Oncol. Rep. 2013;30:2027–2034. doi: 10.3892/or.2013.2728. PubMed DOI PMC

Hwang S.J., Lee H.W., Kim H.R., Song H.J., Lee D.H., Lee H., Shin C.H., Joung J.-G., Kim D.-H., Joo K.M., et al. Overexpression of MicroRNA-95-3p Suppresses Brain Metastasis of Lung Adenocarcinoma through Downregulation of Cyclin D1. Oncotarget. 2015;6:20434–20448. doi: 10.18632/oncotarget.3886. PubMed DOI PMC

Chen L., Xu S., Xu H., Zhang J., Ning J., Wang S. MicroRNA-378 Is Associated with Non-Small Cell Lung Cancer Brain Metastasis by Promoting Cell Migration, Invasion and Tumor Angiogenesis. Med. Oncol. 2012;29:1673–1680. doi: 10.1007/s12032-011-0083-x. PubMed DOI

Arora S., Ranade A.R., Tran N.L., Nasser S., Sridhar S., Korn R.L., Ross J.T.D., Dhruv H., Foss K.M., Sibenaller Z., et al. MicroRNA-328 Is Associated with (Non-Small) Cell Lung Cancer (NSCLC) Brain Metastasis and Mediates NSCLC Migration. Int. J. Cancer. 2011;129:2621–2631. doi: 10.1002/ijc.25939. PubMed DOI PMC

Wang H., Deng Q., Lv Z., Ling Y., Hou X., Chen Z., Dinglin X., Ma S., Li D., Wu Y., et al. N6-Methyladenosine Induced MiR-143-3p Promotes the Brain Metastasis of Lung Cancer via Regulation of VASH1. Mol. Cancer. 2019;18:181. doi: 10.1186/s12943-019-1108-x. PubMed DOI PMC

Liu J.-K., Liu H.-F., Ding Y., Gao G.-D. Predictive Value of MicroRNA Let-7a Expression for Efficacy and Prognosis of Radiotherapy in Patients with Lung Cancer Brain Metastasis: A Case–Control Study. Medicine. 2018;97:e12847. doi: 10.1097/MD.0000000000012847. PubMed DOI PMC

Wei C., Zhang R., Cai Q., Gao X., Tong F., Dong J., Hu Y., Wu G., Dong X. MicroRNA-330-3p Promotes Brain Metastasis and Epithelial-Mesenchymal Transition via GRIA3 in Non-Small Cell Lung Cancer. Aging. 2019;11:6734–6761. doi: 10.18632/aging.102201. PubMed DOI PMC

Chen L., Li X., Zhao Y., Liu W., Wu H., Liu J., Mu X., Wu H. Down-Regulated MicroRNA-375 Expression as a Predictive Biomarker in Non-Small Cell Lung Cancer Brain Metastasis and Its Prognostic Significance. Pathol. Res. Pract. 2017;213:882–888. doi: 10.1016/j.prp.2017.06.012. PubMed DOI

Wu D., Deng S., Li L., Liu T., Zhang T., Li J., Yu Y., Xu Y. TGF-Β1-Mediated Exosomal Lnc-MMP2-2 Increases Blood–Brain Barrier Permeability via the MiRNA-1207-5p/EPB41L5 Axis to Promote Non-Small Cell Lung Cancer Brain Metastasis. Cell Death Dis. 2021;12:721. doi: 10.1038/s41419-021-04004-z. PubMed DOI PMC

Mouttet D., Laé M., Caly M., Gentien D., Carpentier S., Peyro-Saint-Paul H., Vincent-Salomon A., Rouzier R., Sigal-Zafrani B., Sastre-Garau X., et al. Estrogen-Receptor, Progesterone-Receptor and HER2 Status Determination in Invasive Breast Cancer. Concordance between Immuno-Histochemistry and MapQuant™ Microarray Based Assay. PLoS ONE. 2016;11:e0146474. doi: 10.1371/journal.pone.0146474. PubMed DOI PMC

Berman A.T., Thukral A.D., Hwang W.-T., Solin L.J., Vapiwala N. Incidence and Patterns of Distant Metastases for Patients With Early-Stage Breast Cancer After Breast Conservation Treatment. Clin. Breast Cancer. 2013;13:88–94. doi: 10.1016/j.clbc.2012.11.001. PubMed DOI

Saha A., Ghosh S., Roy C., Choudhury K., Chakrabarty B., Sarkar R. Demographic and Clinical Profile of Patients with Brain Metastases: A Retrospective Study. Asian J. Neurosurg. 2013;8:157. doi: 10.4103/1793-5482.121688. PubMed DOI PMC

Wilhelm I., Molnár J., Fazakas C., Haskó J., Krizbai I. Role of the Blood-Brain Barrier in the Formation of Brain Metastases. Int. J. Mol. Sci. 2013;14:1383–1411. doi: 10.3390/ijms14011383. PubMed DOI PMC

Kennecke H., Yerushalmi R., Woods R., Cheang M.C.U., Voduc D., Speers C.H., Nielsen T.O., Gelmon K. Metastatic Behavior of Breast Cancer Subtypes. J. Clin. Oncol. 2010;28:3271–3277. doi: 10.1200/JCO.2009.25.9820. PubMed DOI

Sereno M., Haskó J., Molnár K., Medina S.J., Reisz Z., Malhó R., Videira M., Tiszlavicz L., Booth S.A., Wilhelm I., et al. Downregulation of Circulating MiR 802-5p and MiR 194-5p and Upregulation of Brain MEF2C along Breast Cancer Brain Metastasization. Mol. Oncol. 2020;14:520–538. doi: 10.1002/1878-0261.12632. PubMed DOI PMC

Figueira I., Godinho-Pereira J., Galego S., Maia J., Haskó J., Molnár K., Malhó R., Costa-Silva B., Wilhelm I., Krizbai I.A., et al. MicroRNAs and Extracellular Vesicles as Distinctive Biomarkers of Precocious and Advanced Stages of Breast Cancer Brain Metastases Development. Int. J. Mol. Sci. 2021;22:5214. doi: 10.3390/ijms22105214. PubMed DOI PMC

Debeb B.G., Lacerda L., Anfossi S., Diagaradjane P., Chu K., Bambhroliya A., Huo L., Wei C., Larson R.A., Wolfe A.R., et al. MiR-141-Mediated Regulation of Brain Metastasis From Breast Cancer. J. Natl. Cancer Inst. 2016;108:djw026. doi: 10.1093/jnci/djw026. PubMed DOI PMC

Okuda H., Xing F., Pandey P.R., Sharma S., Watabe M., Pai S.K., Mo Y.-Y., Iiizumi-Gairani M., Hirota S., Liu Y., et al. MiR-7 Suppresses Brain Metastasis of Breast Cancer Stem-Like Cells By Modulating KLF4. Cancer Res. 2013;73:1434–1444. doi: 10.1158/0008-5472.CAN-12-2037. PubMed DOI PMC

Hwang S.J., Seol H.J., Park Y.M., Kim K.H., Gorospe M., Nam D.-H., Kim H.H. MicroRNA-146a Suppresses Metastatic Activity in Brain Metastasis. Mol. Cells. 2012;34:329–334. doi: 10.1007/s10059-012-0171-6. PubMed DOI PMC

Xing F., Sharma S., Liu Y., Mo Y.-Y., Wu K., Zhang Y.-Y., Pochampally R., Martinez L.A., Lo H.-W., Watabe K. MiR-509 Suppresses Brain Metastasis of Breast Cancer Cells by Modulating RhoC and TNF-α. Oncogene. 2015;34:4890–4900. doi: 10.1038/onc.2014.412. PubMed DOI PMC

Pan J.-K., Lin C.-H., Kuo Y.-L., Ger L.-P., Cheng H.-C., Yao Y.-C., Hsiao M., Lu P.-J. MiR-211 Determines Brain Metastasis Specificity through SOX11/NGN2 Axis in Triple-Negative Breast Cancer. Oncogene. 2021;40:1737–1751. doi: 10.1038/s41388-021-01654-3. PubMed DOI PMC

Tominaga N., Kosaka N., Ono M., Katsuda T., Yoshioka Y., Tamura K., Lötvall J., Nakagama H., Ochiya T. Brain Metastatic Cancer Cells Release MicroRNA-181c-Containing Extracellular Vesicles Capable of Destructing Blood–Brain Barrier. Nat. Commun. 2015;6:6716. doi: 10.1038/ncomms7716. PubMed DOI PMC

Xing F., Liu Y., Wu S.-Y., Wu K., Sharma S., Mo Y.-Y., Feng J., Sanders S., Jin G., Singh R., et al. Loss of XIST in Breast Cancer Activates MSN-c-Met and Reprograms Microglia via Exosomal MiRNA to Promote Brain Metastasis. Cancer Res. 2018;78:4316–4330. doi: 10.1158/0008-5472.CAN-18-1102. PubMed DOI PMC

Fong M.Y., Zhou W., Liu L., Alontaga A.Y., Chandra M., Ashby J., Chow A., O’Connor S.T.F., Li S., Chin A.R., et al. Breast-Cancer-Secreted MiR-122 Reprograms Glucose Metabolism in Premetastatic Niche to Promote Metastasis. Nat. Cell Biol. 2015;17:183–194. doi: 10.1038/ncb3094. PubMed DOI PMC

Abbas O., Miller D.D., Bhawan J. Cutaneous Malignant Melanoma: Update on Diagnostic and Prognostic Biomarkers. Am. J. Dermatopathol. 2014;36:363–379. doi: 10.1097/DAD.0b013e31828a2ec5. PubMed DOI

Knoll S., Fürst K., Kowtharapu B., Schmitz U., Marquardt S., Wolkenhauer O., Martin H., Pützer B.M. E2F1 Induces MiR-224/452 Expression to Drive EMT through TXNIP Downregulation. EMBO Rep. 2014;15:1315–1329. doi: 10.15252/embr.201439392. PubMed DOI PMC

Rang Z., Yang G., Wang Y., Cui F. MiR-542-3p Suppresses Invasion and Metastasis by Targeting the Proto-Oncogene Serine/Threonine Protein Kinase, PIM1, in Melanoma. Biochem. Biophys. Res. Commun. 2016;474:315–320. doi: 10.1016/j.bbrc.2016.04.093. PubMed DOI

Mikkelsen L.H., Andersen M.K., Andreasen S., Larsen A.-C., Tan Q., Toft P.B., Wadt K., Heegaard S. Global MicroRNA Profiling of Metastatic Conjunctival Melanoma. Melanoma Res. 2019;29:465–473. doi: 10.1097/CMR.0000000000000606. PubMed DOI

Bustos M.A., Tran K.D., Rahimzadeh N., Gross R., Lin S.Y., Shoji Y., Murakami T., Boley C.L., Tran L.T., Cole H., et al. Integrated Assessment of Circulating Cell-Free MicroRNA Signatures in Plasma of Patients with Melanoma Brain Metastasis. Cancers. 2020;12:1692. doi: 10.3390/cancers12061692. PubMed DOI PMC

Yang X., Zhao H., Yang J., Ma Y., Liu Z., Li C., Wang T., Yan Z., Du N. MiR-150-5p Regulates Melanoma Proliferation, Invasion and Metastasis via SIX1-Mediated Warburg Effect. Biochem. Biophys. Res. Commun. 2019;515:85–91. doi: 10.1016/j.bbrc.2019.05.111. PubMed DOI

Hanniford D., Zhong J., Koetz L., Gaziel-Sovran A., Lackaye D.J., Shang S., Pavlick A., Shapiro R., Berman R., Darvishian F., et al. A MiRNA-Based Signature Detected in Primary Melanoma Tissue Predicts Development of Brain Metastasis. Clin. Cancer Res. 2015;21:4903–4912. doi: 10.1158/1078-0432.CCR-14-2566. PubMed DOI PMC

Tan W.-S., Ho K.-S., Eu K.-W. Brain Metastases in Colorectal Cancers. World J. Surg. 2009;33:817–821. doi: 10.1007/s00268-009-9919-3. PubMed DOI

Li Z., Gu X., Fang Y., Xiang J., Chen Z. MicroRNA Expression Profiles in Human Colorectal Cancers with Brain Metastases. Oncol. Lett. 2012;3:346–350. doi: 10.3892/ol.2011.497. PubMed DOI PMC

Lee S.-J., Kim S.-J., Seo H.-H., Shin S.-P., Kim D., Park C.-S., Kim K.-T., Kim Y.-H., Jeong J.-S., Kim I.-H. Over-Expression of MiR-145 Enhances the Effectiveness of HSVtk Gene Therapy for Malignant Glioma. Cancer Lett. 2012;320:72–80. doi: 10.1016/j.canlet.2012.01.029. PubMed DOI

Wang J., Li B., Wang C., Luo Y., Zhao M., Chen P. Long Noncoding RNA FOXD2-AS1 Promotes Glioma Cell Cycle Progression and Proliferation through the FOXD2-AS1/MiR-31/CDK1 Pathway. J. Cell. Biochem. 2019;120:19784–19795. doi: 10.1002/jcb.29284. PubMed DOI

Kim C.W., Oh E.-T., Kim J.M., Park J.-S., Lee D.H., Lee J.-S., Kim K.K., Park H.J. Corrigendum to “Hypoxia-Induced MicroRNA-590-5p Promotes Colorectal Cancer Progression by Modulating Matrix Metalloproteinase Activity” [Cancer Lett. 416 (2018) 31–41] Cancer Lett. 2019;455:73. doi: 10.1016/j.canlet.2019.04.024. PubMed DOI

Ljungberg B., Albiges L., Abu-Ghanem Y., Bensalah K., Dabestani S., Fernández-Pello S., Giles R.H., Hofmann F., Hora M., Kuczyk M.A., et al. European Association of Urology Guidelines on Renal Cell Carcinoma: The 2019 Update. Eur. Urol. 2019;75:799–810. doi: 10.1016/j.eururo.2019.02.011. PubMed DOI

Jonasch E., Gao J., Rathmell W.K. Renal Cell Carcinoma. BMJ. 2014;349:g4797. doi: 10.1136/bmj.g4797. PubMed DOI PMC

Liu Y., Qi L., Zhang K., Wang F. MicroRNA-10a Suppresses Cell Metastasis by Targeting BDNF and Predicted Patients Survival in Renal Cell Carcinoma. J. BUON Off. J. Balk. Union Oncol. 2021;26:250–258. PubMed

Heinzelmann J., Unrein A., Wickmann U., Baumgart S., Stapf M., Szendroi A., Grimm M.-O., Gajda M.R., Wunderlich H., Junker K. MicroRNAs with Prognostic Potential for Metastasis in Clear Cell Renal Cell Carcinoma: A Comparison of Primary Tumors and Distant Metastases. Ann. Surg. Oncol. 2014;21:1046–1054. doi: 10.1245/s10434-013-3361-3. PubMed DOI

Cai Y., Li H., Zhang Y. Downregulation of MicroRNA-206 Suppresses Clear Cell Renal Carcinoma Proliferation and Invasion by Targeting Vascular Endothelial Growth Factor A. Oncol. Rep. 2016;35:1778–1786. doi: 10.3892/or.2015.4538. PubMed DOI

Song H., Rao Y., Zhang G., Kong X. MicroRNA-384 Inhibits the Growth and Invasion of Renal Cell Carcinoma Cells by Targeting Astrocyte Elevated Gene 1. Oncol. Res. Featur. Preclin. Clin. Cancer Ther. 2018;26:457–466. doi: 10.3727/096504017X15035025554553. PubMed DOI PMC

Dong J.-S., Wu B., Zha Z.-L. MicroRNA-588 Regulates Migration Capacity and Invasiveness of Renal Cancer Cells by Targeting EIF5A2. Eur. Rev. Med. Pharmacol. Sci. 2019;23:10248–10256. doi: 10.26355/eurrev_201912_19662. PubMed DOI

Small RNA Sequencing Identifies a Six-MicroRNA Signature Enabling Classification of Brain Metastases According to their Origin