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Review

MicroRNAs in Body Fluids: A More Promising Biomarker for Clear Cell Renal Cell Carcinoma

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Pages 7663-7675 | Published online: 05 Oct 2021

References

  • Rini BI, Campbell SC, Escudier B. Renal cell carcinoma. Lancet. 2009;373(9669):1119–1132. doi:10.1016/S0140-6736(09)60229-419269025
  • Padala SA, Barsouk A, Thandra KC, et al. Epidemiology of renal cell carcinoma. World J Oncol. 2020;11(3):79–87. doi:10.14740/wjon127932494314
  • Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. doi:10.3322/caac.2149230207593
  • Mytsyk Y, Dosenko V, Borys Y, et al. MicroRNA-15a expression measured in urine samples as a potential biomarker of renal cell carcinoma. Int Urol Nephrol. 2018;50(5):851–859. doi:10.1007/s11255-018-1841-x29549624
  • Aguiari G. MicroRNAs in clear cell renal cell carcinoma: biological functions and applications. J Kidney Cancer VHL. 2015;2(4):140–152. doi:10.15586/jkcvhl.2015.4028326269
  • Jonasch E, Gao J, Rathmell WK. Renal cell carcinoma. BMJ. 2014;349(nov10 11):g4797. doi:10.1136/bmj.g479725385470
  • Rini BI, Atkins MB. Resistance to targeted therapy in renal-cell carcinoma. Lancet Oncol. 2009;10(10):992–1000. doi:10.1016/S1470-2045(09)70240-219796751
  • Bedke J, Albiges L, Capitanio U, et al. The 2021 updated European Association of Urology guidelines on renal cell carcinoma: immune checkpoint inhibitor-based combination therapies for treatment-naive metastatic clear-cell renal cell carcinoma are standard of care. Eur Urol. 2021;80(4):393–397. doi:10.1016/j.eururo.2021.04.04234074559
  • Labriola MK, Batich KA, Zhu J, et al. Immunotherapy is changing first-line treatment of metastatic renal-cell carcinoma. Clin Genitourin Cancer. 2019;17(3):e513–e521. doi:10.1016/j.clgc.2019.01.01730858035
  • Crispen PL, Breau RH, Allmer C, et al. Lymph node dissection at the time of radical nephrectomy for high-risk clear cell renal cell carcinoma: indications and recommendations for surgical templates. Eur Urol. 2011;59(1):18–23. doi:10.1016/j.eururo.2010.08.04220933322
  • Motzer RJ, Russo P. Systemic therapy for renal cell carcinoma. J Urol. 2000;163(2):408–417. doi:10.1016/S0022-5347(05)67889-510647643
  • Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(2):215–233. doi:10.1016/j.cell.2009.01.00219167326
  • Volinia S, Calin GA, Liu CG, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006;103(7):2257–2261. doi:10.1073/pnas.051056510316461460
  • Heinzelmann J, Henning B, Sanjmyatav J, et al. Specific miRNA signatures are associated with metastasis and poor prognosis in clear cell renal cell carcinoma. World J Urol. 2011;29(3):367–373. doi:10.1007/s00345-010-0633-421229250
  • Kosaka N, Iguchi H, Ochiya T. Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci. 2010;101(10):2087–2092. doi:10.1111/j.1349-7006.2010.01650.x20624164
  • Cho WC. MicroRNAs: potential biomarkers for cancer diagnosis, prognosis and targets for therapy. Int J Biochem Cell Biol. 2010;42(8):1273–1281. doi:10.1016/j.biocel.2009.12.01420026422
  • Walmsley SR, McGovern NN, Whyte MK, et al. The HIF/VHL pathway: from oxygen sensing to innate immunity. Am J Respir Cell Mol Biol. 2008;38(3):251–255. doi:10.1165/rcmb.2007-0331TR17932373
  • Gu YZ, Moran SM, Hogenesch JB, et al. Molecular characterization and chromosomal localization of a third alpha-class hypoxia inducible factor subunit, HIF3alpha. Gene Expr. 1998;7(3):205–213.9840812
  • Yu F, White SB, Zhao Q, et al. Dynamic, site-specific interaction of hypoxia-inducible factor-1alpha with the von Hippel-Lindau tumor suppressor protein. Cancer Res. 2001;61(10):4136–4142.11358837
  • Jaakkola P, Mole DR, Tian YM, et al. Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science. 2001;292(5516):468–472. doi:10.1126/science.105979611292861
  • Ivan M, Kondo K, Yang H, et al. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science. 2001;292(5516):464–468. doi:10.1126/science.105981711292862
  • Banumathy G, Cairns P. Signaling pathways in renal cell carcinoma. Cancer Biol Ther. 2010;10(7):658–664. doi:10.4161/cbt.10.7.1324720814228
  • Kaelin WG Jr. The von Hippel-Lindau tumor suppressor protein and clear cell renal carcinoma. Clin Cancer Res. 2007;13(2 Pt 2):680s–684s. doi:10.1158/1078-0432.CCR-06-186517255293
  • Gossage L, Eisen T. Alterations in VHL as potential biomarkers in renal-cell carcinoma. Nat Rev Clin Oncol. 2010;7(5):277–288. doi:10.1038/nrclinonc.2010.4220368728
  • Huang WC, Swietach P, Vaughan-Jones RD, et al. Differentiation impairs low pH-induced Ca2+ signaling and ERK phosphorylation in granule precursor tumour cells. Cell Calcium. 2009;45(4):391–399. doi:10.1016/j.ceca.2009.01.00219249096
  • McCormick RI, Blick C, Ragoussis J, et al. 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. 2013;108(5):1133–1142. doi:10.1038/bjc.2013.5623449350
  • Fasanaro P, Greco S, Lorenzi M, et al. An integrated approach for experimental target identification of hypoxia-induced miR-210. J Biol Chem. 2009;284(50):35134–35143. doi:10.1074/jbc.M109.05277919826008
  • Fedorko M, Pacik D, Wasserbauer R, et al. MicroRNAs in the pathogenesis of renal cell carcinoma and their diagnostic and prognostic utility as cancer biomarkers. Int J Biol Markers. 2016;31(1):e26–37. doi:10.5301/jbm.500017426481440
  • Neal CS, Michael MZ, Rawlings LH, et al. The VHL-dependent regulation of microRNAs in renal cancer. BMC Med. 2010;8(1):64. doi:10.1186/1741-7015-8-6420964835
  • Loncaster JA, Harris AL, Davidson SE, et al. Carbonic anhydrase (CA IX) expression, a potential new intrinsic marker of hypoxia: correlations with tumor oxygen measurements and prognosis in locally advanced carcinoma of the cervix. Cancer Res. 2001;61(17):6394–6399.11522632
  • Gattolliat CH, Couve S, Meurice G, et al. Integrative analysis of dysregulated microRNAs and mRNAs in multiple recurrent synchronized renal tumors from patients with von Hippel-Lindau disease. Int J Oncol. 2018;53(4):1455–1468. doi:10.3892/ijo.2018.449030066860
  • Hell MP, Thoma CR, Fankhauser N, et al. miR-28-5p promotes chromosomal instability in VHL-associated cancers by inhibiting Mad2 translation. Cancer Res. 2014;74(9):2432–2443. doi:10.1158/0008-5472.CAN-13-204124491803
  • Mathew LK, Lee SS, Skuli N, et al. Restricted expression of miR-30c-2-3p and miR-30a-3p in clear cell renal cell carcinomas enhances HIF2alpha activity. Cancer Discov. 2014;4(1):53–60. doi:10.1158/2159-8290.CD-13-029124189146
  • Wu TK, Wei CW, Pan YR, et al. The uremic toxin p-cresyl sulfate induces proliferation and migration of clear cell renal cell carcinoma via microRNA-21/ HIF-1alpha axis signals. Sci Rep. 2019;9(1):3207. doi:10.1038/s41598-019-39646-930824757
  • Liu W, Chen H, Wong N, et al. Pseudohypoxia induced by miR-126 deactivation promotes migration and therapeutic resistance in renal cell carcinoma. Cancer Lett. 2017;394:65–75. doi:10.1016/j.canlet.2017.02.02528257806
  • Ma X, Shen D, Li H, et al. MicroRNA-185 inhibits cell proliferation and induces cell apoptosis by targeting VEGFA directly in von Hippel-Lindau-inactivated clear cell renal cell carcinoma. Urol Oncol. 2015;33(4):169 e161–111. doi:10.1016/j.urolonc.2015.01.00325700976
  • Kim WY, Kaelin WG. Role of VHL gene mutation in human cancer. J Clin Oncol. 2004;22(24):4991–5004. doi:10.1200/JCO.2004.05.06115611513
  • Solomon D, Schwartz A. Renal pathology in von Hippel-Lindau disease. Hum Pathol. 1988;19(9):1072–1079. doi:10.1016/s0046-8177(88)80089-33417291
  • Heitzer E, Haque IS, Roberts CES, et al. Current and future perspectives of liquid biopsies in genomics-driven oncology. Nat Rev Genet. 2019;20(2):71–88. doi:10.1038/s41576-018-0071-530410101
  • Wang X, Wang T, Chen C, et al. Serum exosomal miR-210 as a potential biomarker for clear cell renal cell carcinoma. J Cell Biochem. 2018. doi:10.1002/jcb.27347
  • von Brandenstein M, Pandarakalam JJ, Kroon L, et al. MicroRNA 15a, inversely correlated to PKCalpha, is a potential marker to differentiate between benign and malignant renal tumors in biopsy and urine samples. Am J Pathol. 2012;180(5):1787–1797. doi:10.1016/j.ajpath.2012.01.01422429968
  • Shinden Y, Akiyoshi S, Ueo H, et al. Diminished expression of MiR-15a is an independent prognostic marker for breast cancer cases. Anticancer Res. 2015;35(1):123–127.25550542
  • Zhu K, He Y, Xia C, et al. MicroRNA-15a inhibits proliferation and induces apoptosis in CNE1 nasopharyngeal carcinoma cells. Oncol Res. 2016;24(3):145–151. doi:10.3727/096504016X1461196314229027458095
  • Li G, Zhao A, Peoch M, et al. Detection of urinary cell-free miR-210 as a potential tool of liquid biopsy for clear cell renal cell carcinoma. Urol Oncol. 2017;35(5):294–299. doi:10.1016/j.urolonc.2016.12.00728089386
  • Petrozza V, Pastore AL, Palleschi G, et al. Secreted miR-210-3p as non-invasive biomarker in clear cell renal cell carcinoma. Oncotarget. 2017;8(41):69551–69558. doi:10.18632/oncotarget.1844929050224
  • Petrozza V, Costantini M, Tito C, et al. Emerging role of secreted miR-210-3p as potential biomarker for clear cell renal cell carcinoma metastasis. Cancer Biomark. 2020;27(2):181–188. doi:10.3233/CBM-19024231771042
  • Di Meo A, Brown MD, Finelli A, et al. Prognostic urinary miRNAs for the assessment of small renal masses. Clin Biochem. 2020;75:15–22. doi:10.1016/j.clinbiochem.2019.10.002.31672647
  • Wang C, Cai L, Liu J, et al. MicroRNA-30a-5p inhibits the growth of renal cell carcinoma by modulating GRP78 expression. Cell Physiol Biochem. 2017;43(6):2405–2419. doi:10.1159/00048439429073630
  • Zheng B, Zhu H, Gu D, et al. MiRNA-30a-mediated autophagy inhibition sensitizes renal cell carcinoma cells to sorafenib. Biochem Biophys Res Commun. 2015;459(2):234–239. doi:10.1016/j.bbrc.2015.02.08425712526
  • Outeiro-Pinho G, Barros-Silva D, Aznar E, et al. MicroRNA-30a-5p(me): a novel diagnostic and prognostic biomarker for clear cell renal cell carcinoma in tissue and urine samples. J Exp Clin Cancer Res. 2020;39(1):98. doi:10.1186/s13046-020-01600-332487203
  • Chen X, Ba Y, Ma L, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18(10):997–1006. doi:10.1038/cr.2008.28218766170
  • Tusong H, Maolakuerban N, Guan J, et al. Functional analysis of serum microRNAs miR-21 and miR-106a in renal cell carcinoma. Cancer Biomark. 2017;18(1):79–85. doi:10.3233/CBM-16067627814278
  • Huang G, Li H, Wang J, et al. Combination of tumor suppressor miR-20b-5p, miR-30a-5p, and miR-196a-5p as a serum diagnostic panel for renal cell carcinoma. Pathol Res Pract. 2020;216(11):153152. doi:10.1016/j.prp.2020.15315232823234
  • Heinemann FG, Tolkach Y, Deng M, et al. Serum miR-122-5p and miR-206 expression: non-invasive prognostic biomarkers for renal cell carcinoma. Clin Epigenetics. 2018;10(1):11. doi:10.1186/s13148-018-0444-929410711
  • Liu S, Deng X, Zhang J. Identification of dysregulated serum miR-508-3p and miR-885-5p as potential diagnostic biomarkers of clear cell renal carcinoma. Mol Med Rep. 2019;20(6):5075–5083. doi:10.3892/mmr.2019.1076231661117
  • Zhao L, Liu K, Pan X, et al. miR-625-3p promotes migration and invasion and reduces apoptosis of clear cell renal cell carcinoma. Am J Transl Res. 2019;11(10):6475–6486.31737199
  • Pigati L, Yaddanapudi SCS, Iyengar R, et al. Selective release of microRNA species from normal and malignant mammary epithelial cells. PLoS One. 2010;5(10):e13515. doi:10.1371/journal.pone.001351520976003
  • Wang K, Yuan Y, Cho JH, et al. Comparing the MicroRNA spectrum between serum and plasma. PLoS One. 2012;7(7):e41561. doi:10.1371/journal.pone.004156122859996
  • Lou N, Ruan AM, Qiu B, et al. miR-144-3p as a novel plasma diagnostic biomarker for clear cell renal cell carcinoma. Urol Oncol. 2017;35(1):36 e37–36 e14. doi:10.1016/j.urolonc.2016.07.012
  • Chanudet E, Wozniak MB, Bouaoun L, et al. Large-scale genome-wide screening of circulating microRNAs in clear cell renal cell carcinoma reveals specific signatures in late-stage disease. Int J Cancer. 2017;141(9):1730–1740. doi:10.1002/ijc.3084528639257
  • Wang XG, Zhu YW, Wang T, et al. MiR-483-5p downregulation contributed to cell proliferation, metastasis, and inflammation of clear cell renal cell carcinoma. Kaohsiung J Med Sci. 2020. doi:10.1002/kjm2.12320
  • Lucca I, de Martino M, Hofbauer SL, et al. Comparison of the prognostic value of pretreatment measurements of systemic inflammatory response in patients undergoing curative resection of clear cell renal cell carcinoma. World J Urol. 2015;33(12):2045–2052. doi:10.1007/s00345-015-1559-725894368
  • Ohno Y, Nakashima J, Ohori M, et al. Followup of neutrophil-to-lymphocyte ratio and recurrence of clear cell renal cell carcinoma. J Urol. 2012;187(2):411–417. doi:10.1016/j.juro.2011.10.02622177153
  • Sonoda Y, Warita M, Suzuki T, et al. Proteolipid protein 2 is associated with melanoma metastasis. Oncol Rep. 2010;23(2):371–376.20043097
  • Xiao W, Wang C, Chen K, et al. MiR-765 functions as a tumour suppressor and eliminates lipids in clear cell renal cell carcinoma by downregulating PLP2. EBioMedicine. 2020;51:102622. doi:10.1016/j.ebiom.2019.10262231901870
  • Chen X, Lou N, Ruan A, et al. miR-224/miR-141 ratio as a novel diagnostic biomarker in renal cell carcinoma. Oncol Lett. 2018;16(2):1666–1674. doi:10.3892/ol.2018.887430008851
  • Valadi H, Ekstrom K, Bossios A, et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9(6):654–659. doi:10.1038/ncb159617486113
  • Honegger A, Schilling D, Bastian S, et al. Dependence of intracellular and exosomal microRNAs on viral E6/E7 oncogene expression in HPV-positive tumor cells. PLoS Pathog. 2015;11(3):e1004712. doi:10.1371/journal.ppat.100471225760330
  • Kahlert C, Melo SA, Protopopov A, et al. Identification of double-stranded genomic DNA spanning all chromosomes with mutated KRAS and p53 DNA in the serum exosomes of patients with pancreatic cancer. J Biol Chem. 2014;289(7):3869–3875. doi:10.1074/jbc.C113.53226724398677
  • Bao L, You B, Shi S, et al. Metastasis-associated miR-23a from nasopharyngeal carcinoma-derived exosomes mediates angiogenesis by repressing a novel target gene TSGA10. Oncogene. 2018;37(21):2873–2889. doi:10.1038/s41388-018-0183-629520105
  • Keller S, Sanderson MP, Stoeck A, et al. Exosomes: from biogenesis and secretion to biological function. Immunol Lett. 2006;107(2):102–108. doi:10.1016/j.imlet.2006.09.00517067686
  • Rana S, Malinowska K, Zoller M. Exosomal tumor microRNA modulates premetastatic organ cells. Neoplasia. 2013;15(3):281–295. doi:10.1593/neo.12201023479506
  • Zhang L, Zhang S, Yao J, et al. Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth. Nature. 2015;527(7576):100–104. doi:10.1038/nature1537626479035
  • Li Y, Zheng Q, Bao C, et al. Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis. Cell Res. 2015;25(8):981–984. doi:10.1038/cr.2015.8226138677
  • Butz H, Nofech-Mozes R, Ding Q, et al. Exosomal MicroRNAs are diagnostic biomarkers and can mediate cell-cell communication in renal cell carcinoma. Eur Urol Focus. 2016;2(2):210–218. doi:10.1016/j.euf.2015.11.00628723537
  • Yang C, Robbins PD. The roles of tumor-derived exosomes in cancer pathogenesis. Clin Dev Immunol. 2011;2011:842849. doi:10.1155/2011/84284922190973
  • Zhang W, Ni M, Su Y, et al. MicroRNAs in serum exosomes as potential biomarkers in clear-cell renal cell carcinoma. Eur Urol Focus. 2018;4(3):412–419. doi:10.1016/j.euf.2016.09.00728753793
  • Folkerts H, Wierenga AT, van den Heuvel FA, et al. Elevated VMP1 expression in acute myeloid leukemia amplifies autophagy and is protective against venetoclax-induced apoptosis. Cell Death Dis. 2019;10(6):421. doi:10.1038/s41419-019-1648-431142733
  • Ying Q, Liang L, Guo W, et al. Hypoxia-inducible microRNA-210 augments the metastatic potential of tumor cells by targeting vacuole membrane protein 1 in hepatocellular carcinoma. Hepatology. 2011;54(6):2064–2075. doi:10.1002/hep.2461422144109
  • Crentsil VC, Liu H, Sellitti DF. Comparison of exosomal microRNAs secreted by 786-O clear cell renal carcinoma cells and HK-2 proximal tubule-derived cells in culture identifies microRNA-205 as a potential biomarker of clear cell renal carcinoma. Oncol Lett. 2018;16(1):1285–1290. doi:10.3892/ol.2018.875130061948
  • Xu XW, Li S, Yin F, et al. Expression of miR-205 in renal cell carcinoma and its association with clinicopathological features and prognosis. Eur Rev Med Pharmacol Sci. 2018;22(3):662–670. doi:10.26355/eurrev_201802_1429129461593
  • Koren E, Fuchs Y. The bad seed: cancer stem cells in tumor development and resistance. Drug Resist Updat. 2016;28:1–12. doi:10.1016/j.drup.2016.06.00627620951
  • Vahidian F, Mohammadi H, Ali-Hasanzadeh M, et al. MicroRNAs and breast cancer stem cells: potential role in breast cancer therapy. J Cell Physiol. 2019;234(4):3294–3306. doi:10.1002/jcp.2724630362508
  • Wang L, Yang G, Zhao D, et al. CD103-positive CSC exosome promotes EMT of clear cell renal cell carcinoma: role of remote MiR-19b-3p. Mol Cancer. 2019;18(1):86. doi:10.1186/s12943-019-0997-z30975145
  • Song S, Long M, Yu G, et al. Urinary exosome miR-30c-5p as a biomarker of clear cell renal cell carcinoma that inhibits progression by targeting HSPA5. J Cell Mol Med. 2019;23(10):6755–6765. doi:10.1111/jcmm.1455331342628
  • Yang GH, Li S, Pestka JJ. Down-regulation of the endoplasmic reticulum chaperone GRP78/BiP by vomitoxin (deoxynivalenol). Toxicol Appl Pharmacol. 2000;162(3):207–217. doi:10.1006/taap.1999.884210652249
  • Xiao CT, Lai WJ, Zhu WA, et al. MicroRNA derived from circulating exosomes as noninvasive biomarkers for diagnosing renal cell carcinoma. Onco Targets Ther. 2020;13:10765–10774. doi:10.2147/OTT.S27160633122915
  • Sun B, Zhang J, Liu M, et al. Alkannin inhibits proliferation, migration and invasion of hepatocellular carcinoma cells via regulation of miR-92a. Biomed Pharmacother. 2019;114:108782. doi:10.1016/j.biopha.2019.10878230909147
  • Si H, Sun X, Chen Y, et al. Circulating microRNA-92a and microRNA-21 as novel minimally invasive biomarkers for primary breast cancer. J Cancer Res Clin Oncol. 2013;139(2):223–229. doi:10.1007/s00432-012-1315-y23052693
  • Shi Y, Liu Z. Serum miR-92a-1 is a novel diagnostic biomarker for colorectal cancer. J Cell Mol Med. 2020;24(15):8363–8367. doi:10.1111/jcmm.1528232562465
  • Cui Y, Yang J, Bai Y, et al. miR-424-5p regulates cell proliferation and migration of esophageal squamous cell carcinoma by targeting SIRT4. J Cancer. 2020;11(21):6337–6347. doi:10.7150/jca.5058733033517
  • Liu X, Fu Y, Zhang G, et al. miR-424-5p promotes anoikis resistance and lung metastasis by inactivating hippo signaling in thyroid cancer. Mol Ther Oncol. 2019;15:248–260. doi:10.1016/j.omto.2019.10.008
  • Jin L, Li Y, Liu J, et al. Tumor suppressor miR-149-5p is associated with cellular migration, proliferation and apoptosis in renal cell carcinoma. Mol Med Rep. 2016;13(6):5386–5392. doi:10.3892/mmr.2016.520527121091
  • Guo P, Sheng M, Liu H, et al. Effects of miR-218-1-3p and miR-149 on proliferation and apoptosis of non-small cell lung cancer cells. Oncol Lett. 2020;20(4):96. doi:10.3892/ol.2020.1195732831915
  • Youssef YM, White NM, Grigull J, et al. Accurate molecular classification of kidney cancer subtypes using microRNA signature. Eur Urol. 2011;59(5):721–730. doi:10.1016/j.eururo.2011.01.00421272993
  • Qi Y, Wang L, Wang K, et al. New mechanistic insights of clear cell renal cell carcinoma from integrated miRNA and mRNA expression profiling studies. Biomed Pharmacother. 2019;111:821–834. doi:10.1016/j.biopha.2018.12.09930616081
  • Nie W, Ni D, Ma X, et al. miR122 promotes proliferation and invasion of clear cell renal cell carcinoma by suppressing Forkhead box O3. Int J Oncol. 2019;54(2):559–571. doi:10.3892/ijo.2018.463630483771
  • Lin C, Li Z, Chen P, et al. Oncogene miR-154-5p regulates cellular function and acts as a molecular marker with poor prognosis in renal cell carcinoma. Life Sci. 2018;209:481–489. doi:10.1016/j.lfs.2018.08.04430138594
  • Zhang J, Ye Y, Chang DW, et al. Global and targeted miRNA expression profiling in clear cell renal cell carcinoma tissues potentially links miR-155-5p and miR-210-3p to both tumorigenesis and recurrence. Am J Pathol. 2018;188(11):2487–2496. doi:10.1016/j.ajpath.2018.07.02630201497
  • Ralla B, Busch J, Florcken A, et al. miR-9-5p in nephrectomy specimens is a potential predictor of primary resistance to first-line treatment with tyrosine kinase inhibitors in patients with metastatic renal cell carcinoma. Cancers (Basel). 2018;10(9):321. doi:10.3390/cancers10090321
  • Garrigos C, Molina-Pinelo S, Melendez R, et al. MicroRNAs as potential predictors of extreme response to tyrosine kinase inhibitors in renal cell cancer. Urol Oncol. 2020;38(7):640 e623–640 e629. doi:10.1016/j.urolonc.2020.01.012
  • Incorvaia L, Fanale D, Badalamenti G, et al. A “lymphocyte MicroRNA signature” as predictive biomarker of immunotherapy response and plasma pd-1/pd-l1 expression levels in patients with metastatic renal cell carcinoma: pointing towards epigenetic reprogramming. Cancers (Basel). 2020;12(11):3396. doi:10.3390/cancers12113396
  • Qu F, Ye J, Pan X, et al. MicroRNA-497-5p down-regulation increases PD-L1 expression in clear cell renal cell carcinoma. J Drug Target. 2019;27(1):67–74. doi:10.1080/1061186X.2018.147975530183478
  • Tito C, De Falco E, Rosa P, et al. Circulating microRNAs from the molecular mechanisms to clinical biomarkers: a focus on the clear cell renal cell carcinoma. Genes (Basel). 2021;12(8):1154. doi:10.3390/genes1208115434440329
  • Szabo Z, Szegedi K, Gombos K, et al. Expression of miRNA-21 and miRNA-221 in clear cell renal cell carcinoma (ccRCC) and their possible role in the development of ccRCC. Urol Oncol. 2016;34(12):533 e521–533 e527. doi:10.1016/j.urolonc.2016.06.011
  • Liu F, Chen N, Xiao R, et al. 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. 2016;480(1):87–93. doi:10.1016/j.bbrc.2016.10.00427717821
  • Liep J, Kilic E, Meyer HA, et al. Cooperative effect of miR-141-3p and miR-145-5p in the regulation of targets in clear cell renal cell carcinoma. PLoS One. 2016;11(6):e0157801. doi:10.1371/journal.pone.015780127336447
  • Chen B, Duan L, Yin G, et al. Simultaneously expressed miR-424 and miR-381 synergistically suppress the proliferation and survival of renal cancer cells—Cdc2 activity is up-regulated by targeting WEE1. Clinics (Sao Paulo). 2013;68(6):825–833. doi:10.6061/clinics/2013(06)1723778472
  • He Y, Liu J, Wang Y, et al. Role of miR-486-5p in regulating renal cell carcinoma cell proliferation and apoptosis via TGF-beta-activated kinase 1. J Cell Biochem. 2019;120(3):2954–2963. doi:10.1002/jcb.2690030537206
  • Yao D, Xia S, Jin C, et al. Feedback activation of GATA1/miR-885-5p/PLIN3 pathway decreases sunitinib sensitivity in clear cell renal cell carcinoma. Cell Cycle. 2020;19(17):2195–2206. doi:10.1080/15384101.2020.180118932783497