MicroRNAs in the pathogenesis of renal cell carcinoma and their diagnostic and prognostic value

Czech version

Authors: M. Fedorko; D. Pacík; G. Varga; R. Wasserbauer; M. Ghazal; M. Nussir
Published in: Urol List 2015; 13(1): 27-31

Overview

MicroRNAs (miRNA/miRNAs) are short non-coding RNAs that regulate gene expression at post-transcriptional level. They are involved in a number of critical biological processes including carcinogenesis. In the pathogenesis of renal cell carcinoma (RCC) they can act both as oncogenes and tumor suppressors. They regulate apoptosis, cell growth, migration, invasion, proliferation, colony formation or angiogenesis through target proteins involved in several signaling pathways and they are directly involved in mechanisms of hypoxia and epithelial-to-mesenchymal transition. Differentially expressed miRNAs can differentiate tumor tissue from healthy renal tissue and even different RCC subtypes. Circulating and urinary miRNAs could become biomarkers for non-invasive diagnosis or detection of the relapse of RCC. Moreover, prognostic value of several miRNAs has been shown. They may help identify high-risk primary tumors and estimate treatment response to biological treatment in metastatic tumors. The aim of the article is to provide comprehensive and the most up-to-date information about the role of miRNAs in the pathogenesis of RCC and their diagnostic/prognostic value.

Key words:
microRNA, renal cell carcinoma, biomarker, pathogenesis, diagnosis, prognosis

Sources

1. GLOBOCAN 2012: estimated cancer incidence, mortality and prevalence worldwide in 2012. International Agency for Research on Cancer. WHO. [online]. Available from: http://globocan.iarc.fr.

2. National Cancer Institute. Surveillance, epidemiology and end results program. [online]. Available from: http://seer.cancer.gov/csr/1975_2010/.

3. Čermák A, Pacík D, Vít V. Současný pohled na léčbu malých nádorů ledvin. Urol List 2012; 10(3): 6–15.

4. Čermák A, Pacík D. Přirozený vývoj karcinomu ledviny. Ces Urol 2001; 5(5): 28.

5. Redova M, Svoboda M, Slaby O. MicroRNAs and their target gene networks in renal cell carcinoma. Biochem Biophys Res Commun 2011; 405(2): 153–156. doi: 10.1016/j.bbrc.2011.01.019.

6. White NM, Yousef GM. MicroRNAs: exploring a new dimension in the pathogenesis of kidney cancer. BMC Med 2010; 8: 65. doi: 10.1186/1741-7015-8-65.

7. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer 2006; 6(11): 857–866.

8. Banumathy G, Cairns P. Signaling pathways in renal cell carcinoma. Cancer Biol Ther 2010; 10(7): 658–664. doi: 10.4161/cbt.10.7.13247.

9. Campbell S, Lane B. Malignant renal tumors. In: Wein AJ, Kavoussi LR, Novick AC et al (eds). Campbell-Walsh Urology. 10. ed. Philadelphia: Saunders 2012: 1413–1474.

10. Neal CS, Michael MZ, Rawlings LH et al. The VHL-dependent regulation of microRNAs in renal cancer. BMC Med 2010; 8: 64. doi: 10.1186/1741-7015-8-64.

11. 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.2013.56.

12. Redova M, Poprach A, Besse A et al. MiR-210 expression in tumor tissue and in vitro effects of its silencing in renal cell carcinoma. Tumour Biol 2013; 34(1): 481–491. doi: 10.1007/s13277-012-0573-2.

13. Lichner Z, Mejia-Guerrero S, Ignacak M et al. Pleiotropic action of renal cell carcinoma-dysregulated miRNAs on hypoxia-related signaling pathways. Am J Pathol 2012; 180(4): 1675–1687. doi: 10.1016/j.ajpath.2011.12.030.

14. Liu H, Brannon AR, Reddy AR et al. Identifying mRNA targets of microRNA dysregulated in cancer: with application to clear cell renal cell carcinoma. BMC Syst Biol 2010; 4: 51. doi: 10.1186/1752-0509-4-51.

15. Yoshino H, Enokida H, Itesako T et al. Epithelial-mesenchymal transition-related microRNA-200s regulate molecular targets and pathways in renal cell carcinoma. J Hum Genet 2013; 58(8): 508–516. doi: 10.1038/jhg.2013.31.

16. Chen X, Wang X, Ruan A et al. miR-141 is a key regulator of renal cell carcinoma proliferation and metastasis by controlling EphA2 expression. Clin Cancer Res 2014; 20(10): 2617–2630. doi: 10.1158/1078-0432.CCR-13-3224.

17. Li X, Xin S, He Z et al. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor PDCD4 and promotes cell transformation, proliferation, and metastasis in renal cell carcinoma. Cell Physiol Biochem 2014; 33(6): 1631–1642. doi: 10.1159/000362946.

18. Zhang H, Guo Y, Shang C et al. miR-21 downregulated TCF21 to inhibit KISS1 in renal cancer. Urology 2012; 80(6): 1298–1302. doi: 10.1016/j.urology.2012.08.013.

19. Dey N, Das F, Ghosh-Choudhury N et al. microRNA-21 governs TORC1 activation in renal cancer cell proliferation and invasion. PLoS One 2012; 7(6): e37366. doi: 10.1371/journal.pone.0037366.

20. Bera A, Ghosh-Choudhury N, Dey N et al. NFκB--mediated cyclin D1 expression by microRNA-21 influences renal cancer cell proliferation. Cell Signal 2013; 25(12): 2575–2586. doi: 10.1016/j.cellsig.2013.08.005.

21. Li S, Chen T, Zhong Z et al. MicroRNA-155 silencing inhibits proliferation and migration and induces apoptosis by upregulating BACH1 in renal cancer cells. Mol Med Rep 2012; 5(4): 949–954. doi: 10.3892/mmr.2012.779.

22. Ueno K, Hirata H, Shahryari V et al. Tumour suppressor microRNA-584 directly targets oncogene Rock-1 and decreases invasion ability in human clear cell renal cell carcinoma. Br J Cancer 2011; 104(2): 308–315. doi: 10.1038/sj.bjc.6606028.

23. White NM, Khella HW, Grigull J et al. miRNA profiling in metastatic renal cell carcinoma reveals a tumour-suppressor effect for miR-215. Br J Cancer 2011; 105(11): 1741–1749. doi: 10.1038/bjc.2011.401.

24. Yamasaki T, Seki N, Yamada Y et al. Tumor suppressive microRNA-138 contributes to cell migration and invasion through its targeting of vimentin in renal cell carcinoma. Int J Oncol 2012; 41(3): 805–817. doi: 10.3892/ijo.2012.1543.

25. Yamamura S, Saini S, Majid S et al. MicroRNA-34a suppresses malignant transformation by targeting c-Myc transcriptional complexes in human renal cell carcinoma. Carcinogenesis 2012; 33(2): 294–300. doi: 10.1093/carcin/bgr286.

26. Sakurai T, Bilim VN, Ugolkov AV et al. The enhancer of zeste homolog 2 (EZH2), a potential therapeutic target, is regulated by miR-101 in renal cancer cells. Biochem Biophys Res Commun 2012; 422(4): 607–614. doi: 10.1016/j.bbrc.2012.05.035.

27. Tsukigi M, Bilim V, Yuuki K et al. Re-expression of miR-199a suppresses renal cancer cell proliferation and survival by targeting GSK-3. Cancer Lett 2012; 315(2): 189–197. doi: 10.1016/j.canlet.2011.10.008.

28. Hirata H, Hinoda Y, Ueno K et al. MicroRNA-1826 directly targets beta-catenin (CTNNB1) and MEK1 (MAP2K1) in VHL-inactivated renal cancer. Carcinogenesis 2012; 33(3): 501–508. doi: 10.1093/carcin/bgr302.

29. Zhao J, Lei T, Xu C et al. MicroRNA-187, down-regulated in clear cell renal cell carcinoma and associated with lower survival, inhibits cell growth and migration though targeting B7-H3. Biochem Biophys Res Commun 2013; 438(2): 439–444. doi: 10.1016/j.bbrc.2013.07.095.

30. Yamada Y, Hidaka H, Seki N et al. Tumor-suppressive microRNA-135a inhibits cancer cell proliferation by targeting the c-MYC oncogene in renal cell carcinoma. Cancer Sci 2013; 104(3): 304–312. doi: 10.1111/cas.12072.

31. Cui L, Zhou H, Zhao H et al. MicroRNA-99a induces G1-phase cell cycle arrest and suppresses tumorigenicity in renal cell carcinoma. BMC Cancer 2012; 12: 546. doi: 10.1186/1471-2407-12-546.

32. Huang QB, Ma X, Zhang X et al. Down-regulated miR-30a in clear cell renal cell carcinoma correlated with tumor hematogenous metastasis by targeting angiogenesis-specific DLL4. PLoS One 2013; 8(6): e67294.

33. Yu Z, Ni L, Chen D et al. Identification of miR-7 as an oncogene in renal cell carcinoma. J Mol Histol 2013; 44(6): 669–677. doi: 10.1007/s10735-013-9516-5.

34. Nakada C, Matsuura K, Tsukamoto Y et al. Genome-wide microRNA expression profiling in renal cell carcinoma: significant down-regulation of miR-141 and miR-200c. J Pathol 2008; 216(4): 418–427. doi: 10.1002/path.2437.

35. Yi Z, Fu Y, Zhao S et al. Differential expression of miRNA patterns in renal cell carcinoma and nontumorous tissues. J Cancer Res Clin Oncol 2010; 136(6): 855–862. doi: 10.1007/s00432-009-0726-x.

36. Juan D, Alexe G, Antes T et al. Identification of a microRNA panel for clear-cell kidney cancer. Urology 2010; 75(4): 835–841. doi: 10.1016/j.urology.2009.10.033.

37. Chow TF, Youssef YM, Lianidou E et al. Differential expression profiling of microRNAs and their potential involvement in renal cell carcinoma pathogenesis. Clin Biochem 2010; 43(1–2): 150–158. doi: 10.1016/j.clinbiochem.2009.07.020.

38. Cheng T, Wang L, Li Y et al. Differential microRNA expression in renal cell carcinoma. Oncol Lett 2013; 6(3): 769–776.

39. Chen X, Ruan A, Wang X et al. miR-129-3p, as a diagnostic and prognostic biomarker for renal cell carcinoma, attenuates cell migration and invasion via downregulating multiple metastasis-related genes. J Cancer Res Clin Oncol 2014; 140(8): 1295–1304. doi: 10.1007/s00432-014-1690-7.

40. 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.2011.01.004.

41. Petillo D, Kort EJ, Anema J et al. MicroRNA profiling of human kidney cancer subtypes. Int J Oncol 2009; 35(1): 109–114.

42. Faragalla H, Youssef YM, Scorilas A et al. The clinical utility of miR-21 as a diagnostic and prognostic marker for renal cell carcinoma. J Mol Diagn 2012; 14(4): 385–392. doi: 10.1016/j.jmoldx.2012.02.003.

43. Wach S, Nolte E, Theil A et al. MicroRNA profiles classify papillary renal cell carcinoma subtypes. Br J Cancer 2013; 109(3): 714–722. doi: 10.1038/bjc.2013.313.

44. Iwamoto H, Kanda Y, Sejima T et al. Serum miR--210 as a potential biomarker of early clear cell renal cell carcinoma. Int J Oncol 2014; 44(1): 53–58. doi: 10.3892/ijo.2013.2169.

45. Zhao A, Li G, Péoc‘h M et al. Serum miR-210 as a novel biomarker for molecular diagnosis of clear cell renal cell carcinoma. Exp Mol Pathol 2013; 94(1): 115–120. doi: 10.1016/j.yexmp.2012.10.005.

46. Wulfken LM, Moritz R, Ohlmann C et al. MicroRNAs in renal cell carcinoma: diagnostic implications of serum miR-1233 levels. PLoS One 2011; 6(9): e25787. doi: 10.1371/journal.pone.0025787.

47. Redova M, Poprach A, Nekvindova J et al. Circulating miR-378 and miR-451 in serum are potential biomarkers for renal cell carcinoma. J Transl Med 2012; 10: 55. doi: 10.1186/1479-5876-10-55.

48. Zhai Q, Zhou L, Zhao C et al. 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 2012; 419(4): 621–626. doi: 10.1016/j.bbrc.2012.02.060.

49. Zhang WB, Pan ZQ, Yang QS et al. Tumor suppressive miR-509-5p contributes to cell migration, proliferation and antiapoptosis in renal cell carcinoma. Ir J Med Sci 2013; 182(4): 621–627. doi: 10.1007/s11845-013-0941-y.

50. Teixeira AL, Ferreira M, Silva J et al. Higher circulating expression levels of miR-221 associated with poor overall survival in renal cell carcinoma patients. Tumour Biol 2014; 35(5): 4057–4066. doi: 10.1007/s13277-013-1531-3.

51. Von Brandenstein M, Pandarakalam JJ, Kroon L et al. MicroRNA 15a, inversely correlated to PKCα, 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.2012.01.014.

52. Vergho D, Kneitz S, Rosenwald A et al. Combination of expression levels of miR-21 and miR-126 is associated with cancer-specific survival in clear-cell renal cell carcinoma. BMC Cancer 2014; 14: 25. doi: 10.1186/1471-2407-14-25.

53. Fritz HK, Lindgren D, Ljungberg B et al. The miR(21/10b) ratio as a prognostic marker in clear cell renal cell carcinoma. Eur J Cancer 2014; 50(10): 1758–1765. doi: 10.1016/j.ejca.2014.03.281.

54. Slaby O, Jancovicova J, Lakomy R et al. Expression of miRNA-106b in conventional renal cell carcinoma is a potential marker for prediction of early metastasis after nephrectomy. J Exp Clin Cancer Res 2010; 29: 90. doi: 10.1186/1756-9966-29-90.

55. 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/s00345-010-0633-4.

56. Heinzelmann J, Unrein A, Wickmann U et al. 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(3): 1046–1054. doi: 10.1245/s10434-013-3361-3.

57. Wu X, Weng L, Li X et al. Identification of a 4-microRNA signature for clear cell renal cell carcinoma metastasis and prognosis. PLoS One 2012; 7(5): e35661. doi: 10.1371/journal.pone.0035661.

58. Slaby O, Redova M, Poprach A et al. Identification of MicroRNAs associated with early relapse after nephrectomy in renal cell carcinoma patients. Genes Chromosomes Cancer 2012; 51(7): 707–716. doi: 10.1002/gcc.21957.

59. Wotschofsky Z, Busch J, Jung M et al. Diagnostic and prognostic potential of differentially expressed miRNAs between metastatic and non-metastatic renal cell carcinoma at the time of nephrectomy. Clin Chim Acta 2013; 416: 5–10. doi: 10.1016/j.cca.2012.11.010.

60. Gámez-Pozo A, Antón-Aparicio LM, Bayona C et al. MicroRNA expression profiling of peripheral blood samples predicts resistance to first-line sunitinib in advanced renal cell carcinoma patients. Neoplasia 2012; 14(12): 1144–1152.

61. Berkers J, Govaere O, Wolter P et al. A possible role for microRNA-141 down-regulation in sunitinib resistant metastatic clear cell renal cell carcinoma through induction of epithelial-to-mesenchymal transition and hypoxia resistance. J Urol 2013; 189(5): 1930–1938. doi: 10.1016/j.juro.2012.11.133.

62. Prior C, Perez-Gracia JL, Garcia-Donas J et al. Identification of tissue microRNAs predictive of sunitinib activity in patients with metastatic renal cell carcinoma. PLoS One 2014; 9(1): e86263. doi: 10.1371/journal.pone.0086263.