Skip to main content

Advertisement

SpringerLink
Log in

Emerging roles of microRNAs and their implications in uveal melanoma

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

Uveal melanoma (UM) is the most common intraocular malignant tumor in adults with an extremely high mortality rate. Genetic and epigenetic dysregulation contribute to the development of UM. Recent discoveries have revealed dysregulation of the expression levels of microRNAs (miRNAs) as one of the epigenetic mechanisms underlying UM tumorigenesis. Based on their roles, miRNAs are characterized as either oncogenic or tumor suppressive. This review focuses on the roles of miRNAs in UM tumorigenesis, diagnosis, and prognosis, as well as their therapeutic potentials. Particularly, the actions of collective miRNAs are summarized with respect to their involvement in major, aberrant signaling pathways that are implicated in the development and progression of UM. Elucidation of the underlying functional mechanisms and biological aspects of miRNA dysregulation in UM is invaluable in the development of miRNA-based therapeutics, which may be used in combination with conventional treatments to improve therapeutic outcomes. In addition, the expression levels of some miRNAs are correlated with UM initiation and progression and, therefore, may be used as biomarkers for diagnosis and prognosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Basile MS, Mazzon E, Fagone P, Longo A, Russo A, Fallico M et al (2019) Immunobiology of uveal melanoma: state of the art and therapeutic targets. Front Oncol 9:1145. https://doi.org/10.3389/fonc.2019.01145

    Article  PubMed  PubMed Central  Google Scholar 

  2. van den Bosch T, Kilic E, Paridaens D, de Klein A (2010) Genetics of uveal melanoma and cutaneous melanoma: two of a kind? Dermatol Res Pract 2010:360136. https://doi.org/10.1155/2010/360136

    Article  PubMed  PubMed Central  Google Scholar 

  3. Pandiani C, Beranger GE, Leclerc J, Ballotti R, Bertolotto C (2017) Focus on cutaneous and uveal melanoma specificities. Genes Dev 31(8):724–743. https://doi.org/10.1101/gad.296962.117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Berus T, Halon A, Markiewicz A, Orlowska-Heitzman J, Romanowska-Dixon B, Clinical DP (2017) Histopathological and cytogenetic prognosticators in. Anticancer Res 37(12):6541–6549. https://doi.org/10.21873/anticanres.12110

    Article  CAS  PubMed  Google Scholar 

  5. Stark MS, Gray ES, Isaacs T, Chen FK, Millward M, McEvoy A et al (2019) A panel of circulating microRNAs detects uveal melanoma with high precision. Transl Vis Sci Technol 8(6):12. https://doi.org/10.1167/tvst.8.6.12

    Article  PubMed  PubMed Central  Google Scholar 

  6. Messineo D, Barile G, Morrone S, La Torre G, Turchetti P, Accetta L et al (2020) Meta-analysis on the utility of radiotherapy for the treatment of ocular melanoma. Clin Ter 170(1):e89–e98. https://doi.org/10.7417/ct.2020.2195

    Article  CAS  PubMed  Google Scholar 

  7. Diener-West M, Reynolds SM, Agugliaro DJ, Caldwell R, Cumming K, Earle JD et al (2005) Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma: collaborative ocular melanoma study group report no. 26. Arch Ophthalmol. 123(12):1639–1643. https://doi.org/10.1001/archopht.123.12.1639

    Article  PubMed  Google Scholar 

  8. Sandinha MT, Farquharson MA, Roberts F (2004) Identification of monosomy 3 in choroidal melanoma by chromosome in situ hybridisation. The Br J Ophthalmol 88(12):1527–1532. https://doi.org/10.1136/bjo.2004.044768

    Article  CAS  PubMed  Google Scholar 

  9. de Lange MJ, Razzaq L, Versluis M, Verlinde S, Dogrusoz M, Bohringer S et al (2015) Distribution of GNAQ and GNA11 mutation signatures in uveal melanoma points to a light dependent mutation mechanism. PLoS ONE 10(9):e0138002. https://doi.org/10.1371/journal.pone.0138002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Versluis M, de Lange MJ, van Pelt SI, Ruivenkamp CA, Kroes WG, Cao J et al (2015) Digital PCR validates 8q dosage as prognostic tool in uveal melanoma. PLoS ONE 10(3):e0116371. https://doi.org/10.1371/journal.pone.0116371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Sharma A, Biswas A, Liu H, Sen S, Paruchuri A, Katsonis P et al (2019) Mutational landscape of the BAP1 locus reveals an intrinsic control to regulate the miRNA network and the binding of protein complexes in uveal melanoma. Cancers. https://doi.org/10.3390/cancers11101600

    Article  PubMed  PubMed Central  Google Scholar 

  12. Ismail IH, Davidson R, Gagné JP, Xu ZZ, Poirier GG, Hendzel MJ (2014) Germline mutations in BAP1 impair its function in DNA double-strand break repair. Cancer Res 74(16):4282–4294. https://doi.org/10.1158/0008-5472.Can-13-3109

    Article  CAS  PubMed  Google Scholar 

  13. Onken MD, Worley LA, Long MD, Duan S, Council ML, Bowcock AM et al (2008) Oncogenic mutations in GNAQ occur early in uveal melanoma. Invest Ophthalmol Vis Sci 49(12):5230–5234. https://doi.org/10.1167/iovs.08-2145

    Article  PubMed  Google Scholar 

  14. Van Raamsdonk CD, Bezrookove V, Green G, Bauer J, Gaugler L, O’Brien JM et al (2009) Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature 457(7229):599–602. https://doi.org/10.1038/nature07586 (Epub 2008/12/17)

    Article  CAS  PubMed  Google Scholar 

  15. Harbour JW, Onken MD, Roberson ED, Duan S, Cao L, Worley LA et al (2010) Frequent mutation of BAP1 in metastasizing uveal melanomas. Science 330(6009):1410–1413. https://doi.org/10.1126/science.1194472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hubbard KB, Hepler JR (2006) Cell signalling diversity of the Gqalpha family of heterotrimeric G proteins. Cell Signal 18(2):135–150. https://doi.org/10.1016/j.cellsig.2005.08.004

    Article  CAS  PubMed  Google Scholar 

  17. Van Raamsdonk CD, Griewank KG, Crosby MB, Garrido MC, Vemula S, Wiesner T et al (2010) Mutations in GNA11 in uveal melanoma. N Engl J Med 363(23):2191–2199. https://doi.org/10.1056/NEJMoa1000584

    Article  PubMed  PubMed Central  Google Scholar 

  18. Lutz S, Freichel-Blomquist A, Yang Y, Rumenapp U, Jakobs KH, Schmidt M et al (2005) The guanine nucleotide exchange factor p63RhoGEF, a specific link between Gq/11-coupled receptor signaling and RhoA. J Biol Chem 280(12):11134–11139. https://doi.org/10.1074/jbc.M411322200

    Article  CAS  PubMed  Google Scholar 

  19. Chua V, Lapadula D, Randolph C, Benovic JL, Wedegaertner PB, Aplin AE (2017) Dysregulated GPCR signaling and therapeutic options in uveal melanoma. Mol Cancer Res 15(5):501–506. https://doi.org/10.1158/1541-7786.MCR-17-0007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Vaque JP, Dorsam RT, Feng X, Iglesias-Bartolome R, Forsthoefel DJ, Chen Q et al (2013) A genome-wide RNAi screen reveals a trio-regulated Rho GTPase circuitry transducing mitogenic signals initiated by G protein-coupled receptors. Mol Cell 49(1):94–108. https://doi.org/10.1016/j.molcel.2012.10.018

    Article  CAS  PubMed  Google Scholar 

  21. Su J, Li H (2015) RAC1 overexpression promotes the proliferation, migration and epithelial-mesenchymal transition of lens epithelial cells. Int J Clin Exp Pathol 8(9):10760–10767

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Yoshida T, Zhang Y, Rivera Rosado LA, Chen J, Khan T, Moon SY et al (2010) Blockade of rac1 activity induces G1 cell cycle arrest or apoptosis in breast cancer cells through downregulation of cyclin D1, survivin, and X-linked inhibitor of apoptosis protein. Mol Cancer Ther. 9(6):1657–1668. https://doi.org/10.1158/1535-7163 (MCT-09-0906)

    Article  PubMed  Google Scholar 

  23. Weber A, Hengge UR, Urbanik D, Markwart A, Mirmohammadsaegh A, Reichel MB et al (2003) Absence of mutations of the BRAF gene and constitutive activation of extracellular-regulated kinase in malignant melanomas of the uvea. Lab Invest 83(12):1771–1776. https://doi.org/10.1097/01.lab.0000101732.89463.29

    Article  CAS  PubMed  Google Scholar 

  24. Patel M, Smyth E, Chapman PB, Wolchok JD, Schwartz GK, Abramson DH et al (2011) Therapeutic implications of the emerging molecular biology of uveal melanoma. Clin Cancer Res 17(8):2087–2100. https://doi.org/10.1158/1078-0432.Ccr-10-3169

    Article  CAS  PubMed  Google Scholar 

  25. Saraiva VS, Caissie AL, Segal L, Edelstein C, Burnier MN Jr (2005) Immunohistochemical expression of phospho-Akt in uveal melanoma. Melanoma Res 15(4):245–250. https://doi.org/10.1097/00008390-200508000-00003

    Article  CAS  PubMed  Google Scholar 

  26. Xia Z, Yang C, Yang X, Wu S, Feng Z, Qu L et al (2019) miR-652 promotes proliferation and migration of uveal melanoma cells by targeting HOXA9. Med Sci Monit 25:8722–8732. https://doi.org/10.12659/msm.917099

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Li Y, Jia R, Ge S (2017) Role of epigenetics in uveal melanoma. Int J Biol Sci 13(4):426–433. https://doi.org/10.7150/ijbs.18331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Hammond SM (2015) An overview of microRNAs. Adv Drug Deliv Rev 87:3–14. https://doi.org/10.1016/j.addr.2015.05.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Bartel DP (2009) microRNAs: target recognition and regulatory functions. Cell 136(2):215–233. https://doi.org/10.1016/j.cell.2009.01.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Gomase VS, Parundekar AN (2009) microRNA: human disease and development. Int J Bioinform Res Appl 5(5):479–500. https://doi.org/10.1504/ijbra.2009.028678

    Article  CAS  PubMed  Google Scholar 

  31. Li Z, Yu X, Shen J, Jiang Y (2015) microRNA dysregulation in uveal melanoma: a new player enters the game. Oncotarget 6(7):4562–4568. https://doi.org/10.18632/oncotarget.2923

    Article  PubMed  PubMed Central  Google Scholar 

  32. Triozzi PL, Achberger S, Aldrich W, Crabb JW, Saunthararajah Y, Singh AD (2016) Association of tumor and plasma microRNA expression with tumor monosomy-3 in patients with uveal melanoma. Clin Epigenetics 8:80. https://doi.org/10.1186/s13148-016-0243-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Bande Rodriguez MF, Fernandez Marta B, Lago Baameiro N, Santiago-Varela M, Silva-Rodriguez P, Blanco-Teijeiro MJ et al (2020) Blood biomarkers of uveal melanoma: current perspectives. Clin Ophthalmol 14:157–169. https://doi.org/10.2147/opth.s199064

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Grillari J, Hackl M, Grillari-Voglauer R (2010) miR-17-92 cluster: ups and downs in cancer and aging. Biogerontology 11(4):501–506. https://doi.org/10.1007/s10522-010-9272-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Mogilyansky E, Rigoutsos I (2013) The miR-17/92 cluster: a comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease. Cell Death Differ 20(12):1603–1614. https://doi.org/10.1038/cdd.2013.125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Zhou J, Jiang J, Wang S, Xia X (2016) Oncogenic role of microRNA20a in human uveal melanoma. Mol Med Rep 14(2):1560–1566. https://doi.org/10.3892/mmr.2016.5433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Achberger S, Aldrich W, Tubbs R, Crabb JW, Singh AD, Triozzi PL (2014) Circulating immune cell and microRNA in patients with uveal melanoma developing metastatic disease. Mol Immunol 58(2):182–186. https://doi.org/10.1016/j.molimm.2013.11.018

    Article  CAS  PubMed  Google Scholar 

  38. Joshi P, Kooshki M, Aldrich W, Varghai D, Zborowski M, Singh AD et al (2016) Expression of natural killer cell regulatory microRNA by uveal melanoma cancer stem cells. Clin Exp Metastasis 33(8):829–838. https://doi.org/10.1007/s10585-016-9815-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Venza M, Visalli M, Beninati C, Benfatto S, Teti D, Venza I (2016) miR-92a-3p and MYCBP2 are involved in MS-275-induced and c-myc-mediated TRAIL-sensitivity in melanoma cells. Int Immunopharmacol 40:235–243. https://doi.org/10.1016/j.intimp.2016.09.004

    Article  CAS  PubMed  Google Scholar 

  40. Dupont J, Renou JP, Shani M, Hennighausen L, LeRoith D (2002) PTEN overexpression suppresses proliferation and differentiation and enhances apoptosis of the mouse mammary epithelium. J Clin Invest 110(6):815–825. https://doi.org/10.1172/jci13829

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Abdel-Rahman MH, Yang Y, Zhou XP, Craig EL, Davidorf FH, Eng C (2006) High frequency of submicroscopic hemizygous deletion is a major mechanism of loss of expression of PTEN in uveal melanoma. J Clin Oncol 24(2):288–295. https://doi.org/10.1200/jco.2005.02.2418

    Article  CAS  PubMed  Google Scholar 

  42. Ling JW, Lu PR, Zhang YB, Jiang S, Zhang ZC (2017) miR-367 promotes uveal melanoma cell proliferation and migration by regulating PTEN. Genet Mol Res. https://doi.org/10.4238/gmr16039067

    Article  PubMed  Google Scholar 

  43. Sun L, Wang Q, Gao X, Shi D, Mi S, Han Q (2015) MicroRNA-454 functions as an oncogene by regulating PTEN in uveal melanoma. FEBS Lett. 589(19 Pt B):2791–2796. https://doi.org/10.1016/j.febslet.2015.08.007

    Article  CAS  PubMed  Google Scholar 

  44. Peng J, Liu H, Liu C (2017) MiR-155 promotes uveal melanoma cell proliferation and invasion by regulating NDFIP1 expression. Technol Cancer Res Treat 16(6):1160–1167. https://doi.org/10.1177/1533034617737923

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Howitt J, Low LH, Putz U, Doan A, Lackovic J, Goh CP et al (2015) Ndfip1 represses cell proliferation by controlling Pten localization and signaling specificity. J Mol Cell Biol 7(2):119–131. https://doi.org/10.1093/jmcb/mjv020

    Article  CAS  PubMed  Google Scholar 

  46. Chana JS, Wilson GD, Cree IA, Alexander RA, Myatt N, Neale M et al (1999) c-myc, p53, and Bcl-2 expression and clinical outcome in uveal melanoma. Br J Ophthalmol 83(1):110–114. https://doi.org/10.1136/bjo.83.1.110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Brantley MA Jr, Harbour JW (2000) Deregulation of the Rb and p53 pathways in uveal melanoma. Am J Pathol 157(6):1795–1801. https://doi.org/10.1016/s0002-9440(10)64817-1

    Article  PubMed  Google Scholar 

  48. Wang YC, Yang X, Wei WB, Xu XL (2018) Role of microRNA-21 in uveal melanoma cell invasion and metastasis by regulating p53 and its downstream protein. Int J Ophthalmol 11(8):1258–1268. https://doi.org/10.18240/ijo.2018.08.03

    Article  PubMed  PubMed Central  Google Scholar 

  49. Zhang L, He X, Li F, Pan H, Huang X, Wen X et al (2018) The miR-181 family promotes cell cycle by targeting CTDSPL, a phosphatase-like tumor suppressor in uveal melanoma. J Exp Clin Cancer Res 37(1):15. https://doi.org/10.1186/s13046-018-0679-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Sun Q, Cong R, Yan H, Gu H, Zeng Y, Liu N et al (2009) Genistein inhibits growth of human uveal melanoma cells and affects microRNA-27a and target gene expression. Oncol Rep 22(3):563–567. https://doi.org/10.3892/or_00000472

    Article  CAS  PubMed  Google Scholar 

  51. Svoronos AA, Engelman DM, Slack FJ (2016) OncomiR or tumor suppressor? the duplicity of microRNAs in cancer. Cancer Res 76(13):3666–3670. https://doi.org/10.1158/0008-5472.Can-16-0359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Peng D, Dong J, Zhao Y, Peng X, Tang J, Chen X et al (2019) miR-142-3p suppresses uveal melanoma by targeting CDC25C, TGFbetaR1, GNAQ, WASL, and RAC1. Cancer Manag Res 11:4729–4742. https://doi.org/10.2147/cmar.s206461

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Levovitz C, Chen D, Ivansson E, Gyllensten U, Finnigan JP, Alshawish S et al (2014) TGFbeta receptor 1: an immune susceptibility gene in HPV-associated cancer. Cancer Res 74(23):6833–6844. https://doi.org/10.1158/0008-5472.Can-14-0602-t

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Hoffmann I, Clarke PR, Marcote MJ, Karsenti E, Draetta G (1993) Phosphorylation and activation of human cdc25-C by cdc2–cyclin B and its involvement in the self-amplification of MPF at mitosis. EMBO J 12(1):53–63

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. Darbon JM, Penary M, Escalas N, Casagrande F, Goubin-Gramatica F, Baudouin C et al (2000) Distinct Chk2 activation pathways are triggered by genistein and DNA-damaging agents in human melanoma cells. J Biol Chem 275(20):15363–15369. https://doi.org/10.1074/jbc.275.20.15363

    Article  CAS  PubMed  Google Scholar 

  56. Turowski P, Franckhauser C, Morris MC, Vaglio P, Fernandez A, Lamb NJ (2003) Functional cdc25C dual-specificity phosphatase is required for S-phase entry in human cells. Mol Biol Cell 14(7):2984–2998. https://doi.org/10.1091/mbc.e02-08-0515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Alekhina O, Burstein E, Billadeau DD (2017) Cellular functions of WASP family proteins at a glance. J Cell Sci 130(14):2235–2241. https://doi.org/10.1242/jcs.199570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Zheng X, Tang H, Zhao X, Sun Y, Jiang Y, Liu Y (2017) Long non-coding RNA FTH1P3 facilitates uveal melanoma cell growth and invasion through miR-224-5p. PLoS ONE 12(11):e0184746. https://doi.org/10.1371/journal.pone.0184746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Krishnamurthy N, Kurzrock R (2018) Targeting the Wnt/beta-catenin pathway in cancer: Update on effectors and inhibitors. Cancer Treat Rev 62:50–60. https://doi.org/10.1016/j.ctrv.2017.11.002

    Article  CAS  PubMed  Google Scholar 

  60. Li Y, Luo JT, Liu YM, Wei WB (2020) miRNA-145/miRNA-205 inhibits proliferation and invasion of uveal melanoma cells by targeting NPR1/CDC42. Int J Ophthalmol 13(5):718–724. https://doi.org/10.18240/ijo.2020.05.04

    Article  PubMed  PubMed Central  Google Scholar 

  61. Maldonado MDM, Dharmawardhane S (2018) Targeting Rac and Cdc42 GTPases in cancer. Cancer Res 78(12):3101–3111. https://doi.org/10.1158/0008-5472.Can-18-0619

    Article  CAS  PubMed  Google Scholar 

  62. Li J, Liu X, Li C, Wang W (2019) miR-224-5p inhibits proliferation, migration, and invasion by targeting PIK3R3/AKT3 in uveal melanoma. J Cell Biochem 120(8):12412–12421. https://doi.org/10.1002/jcb.28507

    Article  CAS  PubMed  Google Scholar 

  63. Vigneri PG, Tirro E, Pennisi MS, Massimino M, Stella S, Romano C et al (2015) The insulin/IGF system in colorectal cancer development and resistance to therapy. Front Oncol 5:230. https://doi.org/10.3389/fonc.2015.00230

    Article  PubMed  PubMed Central  Google Scholar 

  64. Dearth RK, Cui X, Kim HJ, Kuiatse I, Lawrence NA, Zhang X et al (2006) Mammary tumorigenesis and metastasis caused by overexpression of insulin receptor substrate 1 (IRS-1) or IRS-2. Mol Cell Biol 26(24):9302–9314. https://doi.org/10.1128/mcb.00260-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Li Y, Huang Q, Shi X, Jin X, Shen L, Xu X et al (2014) MicroRNA 145 may play an important role in uveal melanoma cell growth by potentially targeting insulin receptor substrate-1. Chin Med J (Engl) 127(8):1410–1416

    CAS  Google Scholar 

  66. Sharma S, Yang B, Xi X, Grotta JC, Aronowski J, Savitz SI (2011) IL-10 directly protects cortical neurons by activating PI-3 kinase and STAT-3 pathways. Brain Res 1373:189–194. https://doi.org/10.1016/j.brainres.2010.11.096

    Article  CAS  PubMed  Google Scholar 

  67. Venza I, Visalli M, Beninati C, Benfatto S, Teti D, Venza M (2015) IL-10Ralpha expression is post-transcriptionally regulated by miR-15a, miR-185, and miR-211 in melanoma. BMC Med Genomics 8:81. https://doi.org/10.1186/s12920-015-0156-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Zhuo B, Li Y, Li Z, Qin H, Sun Q, Zhang F et al (2015) PI3K/Akt signaling mediated Hexokinase-2 expression inhibits cell apoptosis and promotes tumor growth in pediatric osteosarcoma. Biochem Biophys Res Commun 464(2):401–406. https://doi.org/10.1016/j.bbrc.2015.06.092

    Article  CAS  PubMed  Google Scholar 

  69. Liu Y, Huo Y, Wang D, Tai Y, Li J, Pang D et al (2018) MiR-216a-5p/Hexokinase 2 axis regulates uveal melanoma growth through modulation of warburg effect. Biochem Biophys Res Commun 501(4):885–892. https://doi.org/10.1016/j.bbrc.2018.05.069

    Article  CAS  PubMed  Google Scholar 

  70. Granito A, Guidetti E, Gramantieri L (2015) c-MET receptor tyrosine kinase as a molecular target in advanced hepatocellular carcinoma. J Hepatocell Carcinoma 2:29–38. https://doi.org/10.2147/jhc.S77038

    Article  PubMed  PubMed Central  Google Scholar 

  71. Park M, Dean M, Cooper CS, Schmidt M, O'Brien SJ, Blair DG et al (1986) Mechanism of met oncogene activation. Cell 45(6):895–904. https://doi.org/10.1016/0092-8674(86)90564-7

    Article  CAS  PubMed  Google Scholar 

  72. Mallikarjuna K, Pushparaj V, Biswas J, Krishnakumar S (2007) Expression of epidermal growth factor receptor, ezrin, hepatocyte growth factor, and c-Met in uveal melanoma: an immunohistochemical study. Curr Eye Res 32(3):281–290. https://doi.org/10.1080/02713680601161220

    Article  CAS  PubMed  Google Scholar 

  73. Bakalian S, Marshall JC, Logan P, Faingold D, Maloney S, Di Cesare S et al (2008) Molecular pathways mediating liver metastasis in patients with uveal melanoma. Clin Cancer Res 14(4):951–956. https://doi.org/10.1158/1078-0432.Ccr-06-2630

    Article  CAS  PubMed  Google Scholar 

  74. Yan D, Zhou X, Chen X, Hu DN, Dong XD, Wang J et al (2009) MicroRNA-34a inhibits uveal melanoma cell proliferation and migration through downregulation of c-Met. Invest Ophthalmol Vis Sci 50(4):1559–1565. https://doi.org/10.1167/iovs.08-2681

    Article  PubMed  Google Scholar 

  75. Sun L, Bian G, Meng Z, Dang G, Shi D, Mi S (2015) MiR-144 inhibits uveal melanoma cell proliferation and invasion by regulating c-Met expression. PLoS ONE 10(5):e0124428. https://doi.org/10.1371/journal.pone.0124428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Dong F, Lou D (2012) MicroRNA-34b/c suppresses uveal melanoma cell proliferation and migration through multiple targets. Mol Vis 18:537–546

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Amaro A, Croce M, Ferrini S, Barisione G, Gualco M, Perri P et al (2020) Potential onco-suppressive role of miR122 and miR144 in uveal melanoma through ADAM10 and C-Met inhibition. Cancers. https://doi.org/10.3390/cancers12061468

    Article  PubMed  PubMed Central  Google Scholar 

  78. Zhang L, Liao Y, Tang L (2019) MicroRNA-34 family: a potential tumor suppressor and therapeutic candidate in cancer. J Exp Clin Cancer Res 38(1):53. https://doi.org/10.1186/s13046-019-1059-5

    Article  PubMed  PubMed Central  Google Scholar 

  79. Gangemi R, Amaro A, Gino A, Barisione G, Fabbi M, Pfeffer U et al (2014) ADAM10 correlates with uveal melanoma metastasis and promotes in vitro invasion. Pigment Cell Melanoma Res 27(6):1138–1148. https://doi.org/10.1111/pcmr.12306

    Article  CAS  PubMed  Google Scholar 

  80. Yan D, Dong XD, Chen X, Yao S, Wang L, Wang J et al (2012) Role of microRNA-182 in posterior uveal melanoma: regulation of tumor development through MITF, BCL2 and cyclin D2. PLoS ONE 7(7):e40967. https://doi.org/10.1371/journal.pone.0040967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Zhou Y, Zhang L, Fan J, Jia R, Song X, Xu X et al (2015) Let-7b overexpression leads to increased radiosensitivity of uveal melanoma cells. Melanoma Res 25(2):119–126. https://doi.org/10.1097/cmr.0000000000000140

    Article  CAS  PubMed  Google Scholar 

  82. Liu N, Sun Q, Chen J, Li J, Zeng Y, Zhai S et al (2012) MicroRNA-9 suppresses uveal melanoma cell migration and invasion through the NF-kappaB1 pathway. Oncol Rep 28(3):961–968. https://doi.org/10.3892/or.2012.1905

    Article  CAS  PubMed  Google Scholar 

  83. Wu S, Chen H, Han N, Zhang C, Yan H (2019) Long noncoding RNA PVT1 silencing prevents the development of uveal melanoma by impairing microRNA-17-3p-dependent MDM2 upregulation. Invest Ophthalmol Vis Sci 60(14):4904–4914. https://doi.org/10.1167/iovs.19-27704

    Article  PubMed  Google Scholar 

  84. Hou Q, Han S, Yang L, Chen S, Chen J, Ma N et al (2019) The interplay of microRNA-34a, LGR4, EMT-associated factors, and MMP2 in regulating uveal melanoma cells. Invest Ophthalmol Vis Sci 60(13):4503–4510. https://doi.org/10.1167/iovs.18-26477

    Article  CAS  PubMed  Google Scholar 

  85. Liu J, Ma L, Li C, Zhang Z, Yang G, Zhang W (2013) Tumor-targeting TRAIL expression mediated by miRNA response elements suppressed growth of uveal melanoma cells. Mol Oncol 7(6):1043–1055. https://doi.org/10.1016/j.molonc.2013.08.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Chen X, He D, Dong XD, Dong F, Wang J, Wang L et al (2013) MicroRNA-124a is epigenetically regulated and acts as a tumor suppressor by controlling multiple targets in uveal melanoma. Invest Ophthalmol Vis Sci 54(3):2248–2256. https://doi.org/10.1167/iovs.12-10977

    Article  CAS  PubMed  Google Scholar 

  87. Eedunuri VK, Rajapakshe K, Fiskus W, Geng C, Chew SA, Foley C et al (2015) miR-137 targets p160 steroid receptor coactivators SRC1, SRC2, and SRC3 and inhibits cell proliferation. Mol Endocrinol 29(8):1170–1183. https://doi.org/10.1210/me.2015-1080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Chen X, Wang J, Shen H, Lu J, Li C, Hu DN et al (2011) Epigenetics, microRNAs, and carcinogenesis: functional role of microRNA-137 in uveal melanoma. Invest Ophthalmol Vis Sci 52(3):1193–11929. https://doi.org/10.1167/iovs.10-5272

    Article  CAS  PubMed  Google Scholar 

  89. McGill GG, Haq R, Nishimura EK, Fisher DE (2006) c-Met expression is regulated by Mitf in the melanocyte lineage. J Biol Chem 281(15):10365–10373. https://doi.org/10.1074/jbc.M513094200

    Article  CAS  PubMed  Google Scholar 

  90. Foda HD, Zucker S (2001) Matrix metalloproteinases in cancer invasion, metastasis and angiogenesis. Drug Discov Today 6(9):478–482. https://doi.org/10.1016/s1359-6446(01)01752-4

    Article  CAS  PubMed  Google Scholar 

  91. Wu J, Xie N, Xie K, Zeng J, Cheng L, Lei Y et al (2013) GPR48, a poor prognostic factor, promotes tumor metastasis and activates beta-catenin/TCF signaling in colorectal cancer. Carcinogenesis 34(12):2861–2869. https://doi.org/10.1093/carcin/bgt229

    Article  CAS  PubMed  Google Scholar 

  92. Levine AJ, Hu W, Feng Z (2006) The P53 pathway: what questions remain to be explored? Cell Death Differ 13(6):1027–1036. https://doi.org/10.1038/sj.cdd.4401910

    Article  CAS  PubMed  Google Scholar 

  93. Knudsen ES, Wang JY (2010) Targeting the RB-pathway in cancer therapy. Clin Cancer Res 16(4):1094–1099. https://doi.org/10.1158/1078-0432.Ccr-09-0787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. VanArsdale T, Boshoff C, Arndt KT, Abraham RT (2015) Molecular pathways: targeting the cyclin D-CDK4/6 axis for cancer treatment. Clin Cancer Res 21(13):2905–2910. https://doi.org/10.1158/1078-0432.Ccr-14-0816

    Article  CAS  PubMed  Google Scholar 

  95. Harris SL, Levine AJ (2005) The p53 pathway: positive and negative feedback loops. Oncogene 24(17):2899–2908. https://doi.org/10.1038/sj.onc.1208615

    Article  CAS  PubMed  Google Scholar 

  96. Venza M, Dell’Aversana C, Visalli M, Altucci L, Teti D, Venza I (2014) Identification of microRNA expression patterns in cutaneous and uveal melanoma cell lines. Tumori 100(1):e4–7. https://doi.org/10.1700/1430.15828

    Article  PubMed  Google Scholar 

  97. Zhao G, Yin Y, Zhao B (2020) miR-140-5p is negatively correlated with proliferation, invasion, and tumorigenesis in malignant melanoma by targeting SOX4 via the Wnt/beta-catenin and NF-kappaB cascades. J Cell Physiol 235(3):2161–2170. https://doi.org/10.1002/jcp.29122

    Article  CAS  PubMed  Google Scholar 

  98. Ferracin M, Veronese A, Negrini M (2010) Micromarkers: miRNAs in cancer diagnosis and prognosis. Expert Rev Mol Diagn 10(3):297–308. https://doi.org/10.1586/erm.10.11

    Article  CAS  PubMed  Google Scholar 

  99. Yang C, Wei W (2011) The miRNA expression profile of the uveal melanoma. Sci China Life Sci 54(4):351–358. https://doi.org/10.1007/s11427-011-4149-y

    Article  CAS  PubMed  Google Scholar 

  100. Radhakrishnan A, Badhrinarayanan N, Biswas J, Krishnakumar S (2009) Analysis of chromosomal aberration (1, 3, and 8) and association of microRNAs in uveal melanoma. Mol Vis 15:2146–2154

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Londin E, Magee R, Shields CL, Lally SE, Sato T, Rigoutsos I (2020) IsomiRs and tRNA-derived fragments are associated with metastasis and patient survival in uveal melanoma. Pigment Cell Melanoma Res 33(1):52–62. https://doi.org/10.1111/pcmr.12810

    Article  CAS  PubMed  Google Scholar 

  102. Smit KN, Chang J, Derks K, Vaarwater J, Brands T, Verdijk RM et al (2019) Aberrant microRNA expression and its implications for uveal melanoma metastasis. Cancers. https://doi.org/10.3390/cancers11060815

    Article  PubMed  PubMed Central  Google Scholar 

  103. Sisley K, Rennie IG, Parsons MA, Jacques R, Hammond DW, Bell SM et al (1997) Abnormalities of chromosomes 3 and 8 in posterior uveal melanoma correlate with prognosis. Genes Chromosomes Cancer 19(1):22–28. https://doi.org/10.1002/(sici)1098-2264(199705)19:1<22:aid-gcc4>3.0.co;2-2

    Article  CAS  PubMed  Google Scholar 

  104. Venkatesan N, Kanwar J, Deepa PR, Khetan V, Crowley TM, Raguraman R et al (2016) Clinico-pathological association of delineated miRNAs in uveal melanoma with monosomy 3/disomy 3 chromosomal aberrations. PLoS ONE 11(1):e0146128. https://doi.org/10.1371/journal.pone.0146128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Worley LA, Long MD, Onken MD, Harbour JW (2008) Micro-RNAs associated with metastasis in uveal melanoma identified by multiplexed microarray profiling. Melanoma Res 18(3):184–190. https://doi.org/10.1097/CMR.0b013e3282feeac6

    Article  CAS  PubMed  Google Scholar 

  106. Wroblewska JP, Lach MS, Ustaszewski A, Kulcenty K, Ibbs M, Jagiello I et al (2020) The potential role of selected miRNA in uveal melanoma primary tumors as early biomarkers of disease progression. Genes (Basel). https://doi.org/10.3390/genes11030271

    Article  Google Scholar 

  107. Falzone L, Romano GL, Salemi R, Bucolo C, Tomasello B, Lupo G et al (2019) Prognostic significance of deregulated microRNAs in uveal melanomas. Mol Med Rep 19(4):2599–2610. https://doi.org/10.3892/mmr.2019.9949

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Xin X, Zhang Y, Ling F, Wang L, Sheng X, Qin L et al (2019) Identification of a nine-miRNA signature for the prognosis of uveal melanoma. Exp Eye Res 180:242–249. https://doi.org/10.1016/j.exer.2019.01.004

    Article  CAS  PubMed  Google Scholar 

  109. Larsen AC, Holst L, Kaczkowski B, Andersen MT, Manfe V, Siersma VD et al (2014) MicroRNA expression analysis and Multiplex ligation-dependent probe amplification in metastatic and non-metastatic uveal melanoma. Acta Ophthalmol 92(6):541–549. https://doi.org/10.1111/aos.12322

    Article  CAS  PubMed  Google Scholar 

  110. Ragusa M, Barbagallo C, Statello L, Caltabiano R, Russo A, Puzzo L et al (2015) miRNA profiling in vitreous humor, vitreal exosomes and serum from uveal melanoma patients: Pathological and diagnostic implications. Cancer Biol Ther 16(9):1387–1396. https://doi.org/10.1080/15384047.2015.1046021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Russo A, Caltabiano R, Longo A, Avitabile T, Franco LM, Bonfiglio V et al (2016) Increased levels of miRNA-146a in serum and histologic samples of patients with uveal melanoma. Front Pharmacol 7:424. https://doi.org/10.3389/fphar.2016.00424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Caby MP, Lankar D, Vincendeau-Scherrer C, Raposo G, Bonnerot C (2005) Exosomal-like vesicles are present in human blood plasma. Int Immunol 17(7):879–887. https://doi.org/10.1093/intimm/dxh267

    Article  CAS  PubMed  Google Scholar 

  113. Pisitkun T, Shen RF, Knepper MA (2004) Identification and proteomic profiling of exosomes in human urine. Proc Natl Acad Sci USA 101(36):13368–13373. https://doi.org/10.1073/pnas.0403453101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Eldh M, Olofsson Bagge R, Lasser C, Svanvik J, Sjostrand M, Mattsson J et al (2014) MicroRNA in exosomes isolated directly from the liver circulation in patients with metastatic uveal melanoma. BMC Cancer 14:962. https://doi.org/10.1186/1471-2407-14-962

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Vivet-Noguer R, Tarin M, Roman-Roman S, Alsafadi S (2019) Emerging therapeutic opportunities based on current knowledge of uveal melanoma biology. Cancers. https://doi.org/10.3390/cancers11071019

    Article  PubMed  PubMed Central  Google Scholar 

  116. Milan Rois P, Latorre A, Rodriguez Diaz C, Del Moral A, Somoza A (2018) Reprogramming cells for synergistic combination therapy with nanotherapeutics against uveal melanoma. Biomimetics (Basel). https://doi.org/10.3390/biomimetics3040028

    Article  Google Scholar 

  117. Guzman-Villanueva D, El-Sherbiny IM, Herrera-Ruiz D, Vlassov AV, Smyth HD (2012) Formulation approaches to short interfering RNA and MicroRNA: challenges and implications. J Pharm Sci 101(11):4046–4066. https://doi.org/10.1002/jps.23300

    Article  CAS  PubMed  Google Scholar 

  118. Peng B, Chen Y, Leong KW (2015) MicroRNA delivery for regenerative medicine. Adv Drug Deliv Rev 88:108–122. https://doi.org/10.1016/j.addr.2015.05.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Bregoli L, Movia D, Gavigan-Imedio JD, Lysaght J, Reynolds J, Prina-Mello A (2016) Nanomedicine applied to translational oncology: a future perspective on cancer treatment. Nanomedicine 12(1):81–103. https://doi.org/10.1016/j.nano.2015.08.006

    Article  CAS  PubMed  Google Scholar 

  120. Gou Y, Miao D, Zhou M, Wang L, Zhou H, Su G (2018) Bio-inspired protein-based nanoformulations for cancer theranostics. Front Pharmacol 9:421. https://doi.org/10.3389/fphar.2018.00421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Mahajan S, Patharkar A, Kuche K, Maheshwari R, Deb PK, Kalia K et al (2018) Functionalized carbon nanotubes as emerging delivery system for the treatment of cancer. Int J Pharm 548(1):540–558. https://doi.org/10.1016/j.ijpharm.2018.07.027

    Article  CAS  PubMed  Google Scholar 

  122. Tabatabaei SN, Derbali RM, Yang C, Superstein R, Hamel P, Chain JL et al (2019) Co-delivery of miR-181a and melphalan by lipid nanoparticles for treatment of seeded retinoblastoma. J Control Release. https://doi.org/10.1016/j.jconrel.2019.02.014

    Article  PubMed  Google Scholar 

  123. Manzano M, Vallet-Regi M (2018) Mesoporous silica nanoparticles in nanomedicine applications. J Mater Sci Mater Med 29(5):65. https://doi.org/10.1007/s10856-018-6069-x

    Article  CAS  PubMed  Google Scholar 

  124. Pattni BS, Chupin VV, Torchilin VP (2015) New developments in liposomal drug delivery. Chem Rev 115(19):10938–10966. https://doi.org/10.1021/acs.chemrev.5b00046

    Article  CAS  PubMed  Google Scholar 

  125. Dai X, Tan C (2015) Combination of microRNA therapeutics with small-molecule anticancer drugs: mechanism of action and co-delivery nanocarriers. Adv Drug Deliv Rev 81:184–197. https://doi.org/10.1016/j.addr.2014.09.010

    Article  CAS  PubMed  Google Scholar 

  126. Palakurthi S (2015) Challenges in SN38 drug delivery: current success and future directions. Expert Opin Drug Deliv 12(12):1911–1921. https://doi.org/10.1517/17425247.2015.1070142

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Pediatrics, Pharmacology, and Physiology, University of Montréal, Montréal, Québec, H3T 1C5, Canada

    Chun Yang & Pierre Hardy

  2. Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China

    Yuejiao Wang

  3. Research Center of CHU Sainte-Justine, 3175 Côte-Sainte-Catherine, Room 2.17.004, Montréal, Québec, H3T 1C5, Canada

    Pierre Hardy

Authors
  1. Chun Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuejiao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pierre Hardy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pierre Hardy.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, C., Wang, Y. & Hardy, P. Emerging roles of microRNAs and their implications in uveal melanoma. Cell. Mol. Life Sci. 78, 545–559 (2021). https://doi.org/10.1007/s00018-020-03612-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-020-03612-w

Keywords

Search

Navigation