Expression profiles and prognostic value of miRNAs in retinoblastoma

  • Lara Elis Alberici Delsin
  • Karina Bezerra Salomao
  • Julia Alejandra PezukEmail author
  • Maria Sol Brassesco
Review – Cancer Research


Current cure rates for retinoblastoma (RB) are very high in developed countries. Nonetheless, in less privileged places worldwide, delayed diagnosis and refusal to adhere to treatment still endure an obstacle to improve overall patient survival. Thus, the access to consistent biomarkers for diagnosis at an earlier stage may facilitate treatment and improve outcomes. Over recent years, much attention has been focused on miRNAs, key post-transcriptional regulators that when altered, largely contribute to carcinogenesis and tumor progression. Many of the ~ 2500 microRNAs described in humans have shown differential expression profiles in tumors. In this review, we summarize current data about the roles of miRNAs in RB along with their value as diagnostic/prognostic factors using electronic databases such as PubMed. We reviewed the importance of miRNA in RB biology and discussed their implications in clinic intervention. Several miRNAs have pointed out reliable diagnostic and prognostic molecular biomarkers. The emergence of targeted therapies has significantly improved cancer treatment. In the near future, the modulation of miRNAs will represent a good treatment strategy.


miRNA Cancer Children Retinoblastoma Solid tumor Review 


Compliance with ethical standards

Conflict of interest

Authors declare that they have no conflict of interest.

Research involving human participants and/or animals

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. Acunzo M, Romano G, Wernicke D, Croce CM (2015) MicroRNA and cancer—a brief overview. Adv Biol Regul 57:1–9. Google Scholar
  2. AlAli A, Kletke S, Gallie B, Lam W-C (2018) Retinoblastoma for pediatric ophthalmologists. Asia Pac J Ophthalmol 7:160–168. Google Scholar
  3. Bai Y, Bai X, Wang Z, Zhang X, Ruan C, Miao J (2011) MicroRNA-126 inhibits ischemia-induced retinal neovascularization via regulating angiogenic growth factors. Exp Mol Pathol 91:471–477. Google Scholar
  4. Berindan-Neagoe I, Monroig PDC, Pasculli B, Calin GA (2014) MicroRNAome genome: a treasure for cancer diagnosis and therapy. CA Cancer J Clin 64:311–336. Google Scholar
  5. Berry JL, Xu L, Murphree AL, Krishnan S, Stachelek K, Zolfaghari E, McGovern K, Lee TC, Carlsson A, Kuhn P, Kim JW, Cobrinik D, Hicks J (2017) Potential of aqueous humor as a surrogate tumor biopsy for retinoblastoma. JAMA Ophthalmol 135:1221–1230. Google Scholar
  6. Beta M, Venkatesan N, Vasudevan M, Vetrivel U, Khetan V, Krishnakumar S (2013) Identification and insilico analysis of retinoblastoma serum microRNA profile and gene targets towards prediction of novel serum biomarkers. Bioinf Biol Insights 7:BBI.S10501. Google Scholar
  7. Beta M, Khetan V, Chatterjee N, Suganeswari G, Rishi P, Biswas J, Krishnakumar S (2014) EpCAM knockdown alters microRNA expression in retinoblastoma–functional implication of EpCAM regulated miRNA in tumor progression. PLoS One 9:e114800. Google Scholar
  8. Busch M, Große-Kreul J, Wirtz JJ, Beier M, Stephan H, Royer-Pokora B, Metz K, Dünker N (2017) Reduction of the tumorigenic potential of human retinoblastoma cell lines by TFF1 overexpression involves p53/caspase signaling and miR-18a regulation. Int J Cancer 141:549–560. Google Scholar
  9. Canturk S, Qaddoumi I, Khetan V, Ma Z, Furmanchuk A, Antoneli CBG, Sultan I, Kebudi R, Sharma T, Rodriguez-Galindo C, Abramson DH, Chantada GL (2010) Survival of retinoblastoma in less-developed countries impact of socioeconomic and health-related indicators. Br J Ophthalmol 94:1432–1436. Google Scholar
  10. Carvalho INSR, Reis AHO, Dos Santos ACE, Vargas FR (2017) A polymorphism in mir-34b/c as a potential biomarker for early onset of hereditary retinoblastoma. Cancer Biomark 18:313–317. Google Scholar
  11. Castro-Magdonel BE, Orjuela M, Camacho J, García-Chéquer AJ, Cabrera-Muñoz L, Sadowinski-Pine S, Durán-Figueroa N, Orozco-Romero M, de J. Velázquez-Wong AC, Hernández-Ángeles A, Hernández-Galván C, Lara-Molina C, Ponce-Castañeda MV (2017) miRNome landscape analysis reveals a 30 miRNA core in retinoblastoma. BMC Cancer 17:458. Google Scholar
  12. Che X, Qian Y, Li D (2018) Suppression of disheveled-axin domain containing 1 (DIXDC1) by microRNA-186 inhibits the proliferation and invasion of retinoblastoma cells. J Mol Neurosci 64:252–261. Google Scholar
  13. Chen C-Z, Schaffert S, Fragoso R, Loh C (2013) Regulation of immune responses and tolerance: the microRNA perspective. Immunol Rev 253:112–128. Google Scholar
  14. Chintagumpala M, Chevez-Barrios P, Paysse EA, Plon SE, Hurwitz R (2007) Retinoblastoma: review of current management. Oncologist 12:1237–1246. Google Scholar
  15. Chung SH, Gillies M, Yam M, Wang Y, Shen W (2016) Differential expression of microRNAs in retinal vasculopathy caused by selective Müller cell disruption. Sci Rep 6:28993. Google Scholar
  16. Conkrite K, Sundby M, Mukai S, Thomson JM, Mu D, Hammond SM, MacPherson D (2011) miR-17~ 92 cooperates with RB pathway mutations to promote retinoblastoma. Genes Dev 25:1734–1745. Google Scholar
  17. Dalgard CL, Gonzalez M, deNiro JE, O’Brien JM (2009) Differential microRNA-34a expression and tumor suppressor function in retinoblastoma cells. Invest Ophthalmol Vis Sci 50:4542–4551. Google Scholar
  18. Danda R, Krishnan G, Ganapathy K, Krishnan UM, Vikas K, Elchuri S, Chatterjee N, Krishnakumar S (2013) Targeted expression of suicide gene by tissue-specific promoter and microRNA regulation for cancer gene therapy. PLoS One 8:e83398. Google Scholar
  19. de Fougerolles A, Vornlocher H-P, Maraganore J, Lieberman J (2007) Interfering with disease: a progress report on siRNA-based therapeutics. Nat Rev Drug Discov 6:443–453. Google Scholar
  20. Dimaras H, Kimani K, Dimba EAO, Gronsdahl P, White A, Chan HSL, Gallie BL (2012) Retinoblastoma. Lancet 379:1436–1446. Google Scholar
  21. Ding Y, Wu M, Liu J, Wu C, Huang R, Zhu R, Fei J (2014) Seed-targeting anti-miR-21 inhibiting malignant progression of retinoblastoma and analysis of their phosphorylation signaling pathways. Exp Eye Res 122:1–8. Google Scholar
  22. Dismuke WM, Challa P, Navarro I, Stamer WD, Liu Y (2015) Human aqueous humor exosomes. Exp Eye Res 132:73–77. Google Scholar
  23. Drewry MD, Challa P, Kuchtey JG, Navarro I, Helwa I, Hu Y, Mu H, Daniel Stamer W, Kuchtey RW, Liu Y (2018) Differentially expressed microRNAs in the aqueous humor of patients with exfoliation glaucoma or primary open-angle glaucoma. Hum Mol Genet 27:1263–1275. Google Scholar
  24. Follert P, Cremer H, Béclin C (2014) MicroRNAs in brain development and function: a matter of flexibility and stability. Front Mol Neurosci 7:5. Google Scholar
  25. Friedman RC, Farh KK-H, Burge CB, Bartel DP (2009) Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19:92–105. Google Scholar
  26. Garba AO, Mousa SA (2010) Bevasiranib for the treatment of wet, age-related macular degeneration. Ophthalmol Eye Dis 2:75–83. Google Scholar
  27. Gill S-L, O’Neill H, McCoy RJ, Logeswaran S, O’Brien F, Stanton A, Kelly H, Duffy GP (2014) Enhanced delivery of microRNA mimics to cardiomyocytes using ultrasound responsive microbubbles reverses hypertrophy in an in-vitro model. Technol Health Care 22:37–51. Google Scholar
  28. Gui F, Hong Z, You Z, Wu H, Zhang Y (2016) MiR-21 inhibitor suppressed the progression of retinoblastoma via the modulation of PTEN/PI3K/AKT pathway. Cell Biol Int 40:1294–1302. Google Scholar
  29. Gutschner T, Hämmerle M, Eissmann M, Hsu J, Kim Y, Hung G, Revenko A, Arun G, Stentrup M, Gross M, Zörnig M, MacLeod AR, Spector DL, Diederichs S (2013) The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res 73:1180–1189. Google Scholar
  30. Han BW, Li ZH, Liu SF, Han HB, Dong SJ, Zou HJ, Sun RF, Jia J (2016) A comprehensive review of microRNA-related polymorphisms in gastric cancer. Genet Mol Res. Google Scholar
  31. He S-Q, Rehman H, Gong M-G, Zhao Y-Z, Huang Z-Y, Li C-H, Zhang W-G, Chen X-P (2007) Inhibiting survivin expression enhances TRAIL-induced tumoricidal activity in human hepatocellular carcinoma via cell cycle arrest. Cancer Biol Ther 6:1247–1257Google Scholar
  32. Heitzer E, Ulz P, Geigl JB (2015) Circulating tumor DNA as a liquid biopsy for cancer. Clin Chem 61:112–123. Google Scholar
  33. Hodgkinson CP, Kang MH, Dal-Pra S, Mirotsou M, Dzau VJ (2015) MicroRNAs and cardiac regeneration. Circ Res 116:1700–1711. Google Scholar
  34. Hsu S-H, Yu B, Wang X, Lu Y, Schmidt CR, Lee RJ, Lee LJ, Jacob ST, Ghoshal K (2013) Cationic lipid nanoparticles for therapeutic delivery of siRNA and miRNA to murine liver tumor. Nanomedicine 9:1169–1180. Google Scholar
  35. Huang JC, Babak T, Corson TW, Chua G, Khan S, Gallie BL, Hughes TR, Blencowe BJ, Frey BJ, Morris QD (2007) Using expression profiling data to identify human microRNA targets. Nat Methods 4:1045–1049. Google Scholar
  36. Huang J, Yang Y, Fang F, Liu K (2018) MALAT1 modulates the autophagy of retinoblastoma cell through miR-124-mediated stx17 regulation. J Cell Biochem 119:3853–3863. Google Scholar
  37. Hunter MP, Ismail N, Zhang X, Aguda BD, Lee EJ, Yu L, Xiao T, Schafer J, Lee M-LT, Schmittgen TD, Nana-Sinkam SP, Jarjoura D, Marsh CB (2008) Detection of microRNA expression in human peripheral blood microvesicles. PLoS One 3:e3694. Google Scholar
  38. Hurst DR, Edmonds MD, Welch DR (2009) Metastamir: the field of metastasis-regulatory microRNA is spreading. Cancer Res 69:7495–7498. Google Scholar
  39. Janssen HLA, Reesink HW, Lawitz EJ, Zeuzem S, Rodriguez-Torres M, Patel K, van der Meer AJ, Patick AK, Chen A, Zhou Y, Persson R, King BD, Kauppinen S, Levin AA, Hodges MR (2013) Treatment of HCV infection by targeting microRNA. N Engl J Med 368:1685–1694. Google Scholar
  40. Jia M, Wei Z, Liu P, Zhao X (2016) Silencing of ABCG2 by microRNA-3163 inhibits multidrug resistance in retinoblastoma cancer stem cells. J Korean Med Sci 31:836–842. Google Scholar
  41. Jones K, Nourse JP, Keane C, Bhatnagar A, Gandhi MK (2014) Plasma microRNA are disease response biomarkers in classical Hodgkin lymphoma. Clin Cancer Res 20:253–264. Google Scholar
  42. Joseph RR, Venkatraman SS (2017) Drug delivery to the eye: what benefits do nanocarriers offer? Nanomedicine (Lond) 12:683–702. Google Scholar
  43. Kandalam MM, Beta M, Maheswari UK, Swaminathan S, Krishnakumar S (2012) Oncogenic microRNA 17-92 cluster is regulated by epithelial cell adhesion molecule and could be a potential therapeutic target in retinoblastoma. Mol Vis 18:2279–2287Google Scholar
  44. Kim J, Yao F, Xiao Z, Sun Y, Ma L (2018) MicroRNAs and metastasis: small RNAs play big roles. Cancer Metastasis Rev 37:5–15. Google Scholar
  45. Kong YW, Ferland-McCollough D, Jackson TJ, Bushell M (2012) microRNAs in cancer management. Lancet Oncol 13:e249–e258. Google Scholar
  46. Lambertz I, Nittner D, Mestdagh P, Denecker G, Vandesompele J, Dyer MA, Marine J-C (2010) Monoallelic but not biallelic loss of Dicer1 promotes tumorigenesis in vivo. Cell Death Differ 17:633–641. Google Scholar
  47. Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K, Banham AH, Pezzella F, Boultwood J, Wainscoat JS, Hatton CSR, Harris AL (2008) Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol 141:672–675. Google Scholar
  48. Levy D, Aerts I, Michon J, Lumbroso-Le Rouic L, Cellier C, Orbach D (2014) Childhood cancer: progress but prognosis still very unequal. Example of retinoblastoma and high-risk neuroblastoma. Bull Cancer 101:250–257. Google Scholar
  49. Li J, Xu Z-W, Wang K-H, Wang N, Li D-Q, Wang S (2014) Networks of microRNAs and genes in retinoblastomas. Asian Pac J Cancer Prev 14:6631–6636Google Scholar
  50. Li X, Yang L, Shuai T, Piao T, Wang R (2016) MiR-433 inhibits retinoblastoma malignancy by suppressing Notch1 and PAX6 expression. Biomed Pharmacother 82:247–255. Google Scholar
  51. Liang Y, Chen X, Liang Z (2017) MicroRNA-320 regulates autophagy in retinoblastoma by targeting hypoxia inducible factor-1α. Exp Ther Med 14:2367–2372. Google Scholar
  52. Liu K, Huang J, Xie M, Yu Y, Zhu S, Kang R, Cao L, Tang D, Duan X (2014a) MIR34A regulates autophagy and apoptosis by targeting HMGB1 in the retinoblastoma cell. Autophagy 10:442–452. Google Scholar
  53. Liu S-S, Wang Y-S, Sun Y-F, Miao L-X, Wang J, Li Y-S, Liu H-Y, Liu Q-L (2014b) Plasma microRNA-320, microRNA-let-7e and microRNA-21 as novel potential biomarkers for the detection of retinoblastoma. Biomed Rep 2:424–428. Google Scholar
  54. Liu J, Dang L, Li D, Liang C, He X, Wu H, Qian A, Yang Z, Au DWT, Chiang MWL, Zhang B-T, Han Q, Yue KKM, Zhang H, Lv C, Pan X, Xu J, Bian Z, Shang P, Tan W, Liang Z, Guo B, Lu A, Zhang G (2015) A delivery system specifically approaching bone resorption surfaces to facilitate therapeutic modulation of microRNAs in osteoclasts. Biomaterials 52:148–160. Google Scholar
  55. Liu H, Cao B, Zhao Y, Liang H, Hao F (2018a) Upregulated miR-221/222 promotes cell proliferation and invasion and is associated with invasive features in retinoblastoma. Cancer Biomark. Google Scholar
  56. Liu S, Zhang X, Hu C, Wang Y, Xu C (2018b) miR-29a inhibits human retinoblastoma progression by targeting STAT3. Oncol Rep 39:739–746. Google Scholar
  57. Lujambio A, Lowe SW (2012) The microcosmos of cancer. Nature 482:347–355. Google Scholar
  58. Martin A, Jones A, Bryar PJ, Mets M, Weinstein J, Zhang G, Laurie NA (2013a) MicroRNAs-449a and – 449b exhibit tumor suppressive effects in retinoblastoma. Biochem Biophys Res Commun 440:599–603. Google Scholar
  59. Martin J, Bryar P, Mets M, Weinstein J, Jones A, Martin A, Vanin EF, Scholtens D, Costa FF, Soares MB, Laurie NA (2013b) Differentially expressed miRNAs in retinoblastoma. Gene 512:294–299. Google Scholar
  60. McArthur K, Feng B, Wu Y, Chen S, Chakrabarti S (2011) MicroRNA-200b regulates vascular endothelial growth factor-mediated alterations in diabetic retinopathy. Diabetes 60:1314–1323. Google Scholar
  61. Mirakholi M, Mahmoudi T, Heidari M (2013) MicroRNAs horizon in retinoblastoma. Acta Med Iran 51:823–829Google Scholar
  62. Mitra M, Mohanty C, Harilal A, Maheswari UK, Sahoo SK, Krishnakumar S (2012) A novel in vitro three-dimensional retinoblastoma model for evaluating chemotherapeutic drugs. Mol Vis 18:1361–1378Google Scholar
  63. Montoya V, Fan H, Bryar PJ, Weinstein JL, Mets MB, Feng G, Martin J, Martin A, Jiang H, Laurie NA (2015) Novel miRNA-31 and miRNA-200a-mediated regulation of retinoblastoma proliferation. PLoS One 10:e0138366. Google Scholar
  64. Mortuza R, Feng B, Chakrabarti S (2014) miR-195 regulates SIRT1-mediated changes in diabetic retinopathy. Diabetologia 57:1037–1046. Google Scholar
  65. Nair A, Thevenot P, Hu W, Tang L (2008) Nanotechnology in the treatment and detection of intraocular cancers. J Biomed Nanotechnol 4:410–418Google Scholar
  66. Nguyen T, Menocal EM, Harborth J, Fruehauf JH (2008) RNAi therapeutics: an update on delivery. Curr Opin Mol Ther 10:158–167Google Scholar
  67. Nguyen QD, Schachar RA, Nduaka CI, Sperling M, Basile AS, Klamerus KJ, Chi-Burris K, Yan E, Paggiarino DA, Rosenblatt I, Khan A, Aitchison R, Erlich SS, PF-04523655 Study Group (2012) Phase 1 dose-escalation study of a siRNA targeting the RTP801 gene in age-related macular degeneration patients. Eye (Lond) 26:1099–1105. Google Scholar
  68. Nittner D, Lambertz I, Clermont F, Mestdagh P, Köhler C, Nielsen SJ, Jochemsen A, Speleman F, Vandesompele J, Dyer MA, Schramm A, Schulte JH, Marine J-C (2012) Synthetic lethality between Rb, p53 and Dicer or miR-17-92 in retinal progenitors suppresses retinoblastoma formation. Nat Cell Biol 14:958–965. Google Scholar
  69. Papaioannou G, Mirzamohammadi F, Kobayashi T (2014) MicroRNAs involved in bone formation. Cell Mol Life Sci 71:4747–4761. Google Scholar
  70. Peng Y, Croce CM (2016) The role of MicroRNAs in human cancer. Signal Transduct Target Ther 1:15004. Google Scholar
  71. Reddy KB (2015) MicroRNA (miRNA) in cancer. Cancer Cell Int 15:38. Google Scholar
  72. Reis AHO, Vargas FR, Lemos B (2012) More epigenetic hits than meets the eye: microRNAs and genes associated with the tumorigenesis of retinoblastoma. Front Genet 3:284. Google Scholar
  73. Shehata HH, Abou Ghalia AH, Elsayed EK, Ahmed Said AM, Mahmoud SS (2016) Clinical significance of high levels of survivin and transforming growth factor beta-1 proteins in aqueous humor and serum of retinoblastoma patients. J AAPOS Off Publ Am Assoc Pediatr Ophthalmol Strabismus 20:444.e1–444.e9. Google Scholar
  74. Shen F, Mo M-H, Chen L, An S, Tan X, Fu Y, Rezaei K, Wang Z, Zhang L, Fu SW (2014) MicroRNA-21 down-regulates Rb1 expression by targeting PDCD4 in retinoblastoma. J Cancer 5:804–812. Google Scholar
  75. Shields CL, Manjandavida FP, Arepalli S, Kaliki S, Lally SE, Shields JA (2014) Intravitreal melphalan for persistent or recurrent retinoblastoma vitreous seeds: preliminary results. JAMA Ophthalmol 132:319–325. Google Scholar
  76. Short BG (2008) Safety evaluation of ocular drug delivery formulations: techniques and practical considerations. Toxicol Pathol 36:49–62. Google Scholar
  77. Soliman SE, Dimaras H, Souka AA, Ashry MH, Gallie BL (2015) Socioeconomic and psychological impact of treatment for unilateral intraocular retinoblastoma. J Fr Ophtalmol 38:550–558. Google Scholar
  78. Song D, Diao J, Yang Y, Chen Y (2017) MicroRNA-382 inhibits cell proliferation and invasion of retinoblastoma by targeting BDNF-mediated PI3K/AKT signalling pathway. Mol Med Rep 16:6428–6436. Google Scholar
  79. Stamatopoulos B, Van Damme M, Crompot E, Dessars B, El Housni H, Mineur P, Meuleman N, Bron D, Lagneaux L (2015) Opposite prognostic significance of cellular and serum circulating microRNA-150 in patients with chronic lymphocytic leukemia. Mol Med 21:123–133. Google Scholar
  80. Subramanian N, Kanwar JR, Kanwar RK, Krishnakumar S (2015) Blocking the maturation of oncomiRNAs using pri-miRNA-17 ~ 92 aptamer in retinoblastoma. Nucleic Acid Ther 25:47–52. Google Scholar
  81. Sun Z, Zhang A, Jiang T, Du Z, Che C, Wang F (2015) miR-145 suppressed human retinoblastoma cell proliferation and invasion by targeting ADAM19. Int J Clin Exp Pathol 8:14521–14527Google Scholar
  82. Tanaka Y, Tsuda S, Kunikata H, Sato J, Kokubun T, Yasuda M, Nishiguchi KM, Inada T, Nakazawa T (2014) Profiles of extracellular miRNAs in the aqueous humor of glaucoma patients assessed with a microarray system. Sci Rep 4:5089. Google Scholar
  83. Thériault BL, Dimaras H, Gallie BL, Corson TW (2014) The genomic landscape of retinoblastoma: a review. Clin Exp Ophthalmol 42:33–52. Google Scholar
  84. Tivnan A, Orr WS, Gubala V, Nooney R, Williams DE, McDonagh C, Prenter S, Harvey H, Domingo-Fernández R, Bray IM, Piskareva O, Ng CY, Lode HN, Davidoff AM, Stallings RL (2012) Inhibition of neuroblastoma tumor growth by targeted delivery of microRNA-34a using anti-disialoganglioside GD2 coated nanoparticles. PLoS One 7:e38129. Google Scholar
  85. To K-H, Pajovic S, Gallie BL, Thériault BL (2012) Regulation of p14ARF expression by miR-24: a potential mechanism compromising the p53 response during retinoblastoma development. BMC Cancer 12:69. Google Scholar
  86. Traoré F, Sylla F, Togo B, Kamaté B, Diabaté K, Diakité AA, Diall H, Dicko F, Sylla M, Bey P, Desjardins L, Gagnepain-Lacheteau A, Coze C, Harif M, Doz F (2018) Treatment of retinoblastoma in Sub-Saharan Africa: experience of the paediatric oncology unit at Gabriel Toure Teaching Hospital and the Institute of African Tropical Ophthalmology, Bamako, Mali. Pediatr Blood Cancer 65:e27101. Google Scholar
  87. Tsang JS, Ebert MS, van Oudenaarden A (2010) Genome-wide dissection of microRNA functions and cotargeting networks using gene set signatures. Mol Cell 38:140–153. Google Scholar
  88. Urtti A (2006) Challenges and obstacles of ocular pharmacokinetics and drug delivery. Adv Drug Deliv Rev 58:1131–1135. Google Scholar
  89. Venkatesan N, Deepa PR, Khetan V, Krishnakumar S (2015) Computational and in vitro investigation of miRNA-gene regulations in retinoblastoma pathogenesis: miRNA mimics strategy. Bioinf Biol Insights 9:BBI.S21742. Google Scholar
  90. Wang S, Olson EN (2009) AngiomiRs—key regulators of angiogenesis. Curr Opin Genet Dev 19:205–211. Google Scholar
  91. Wang J, Wang X, Wu G, Hou D, Hu Q (2013) MiR-365b-3p, down-regulated in retinoblastoma, regulates cell cycle progression and apoptosis of human retinoblastoma cells by targeting PAX6. FEBS Lett 587:1779–1786. Google Scholar
  92. Wang S, Cao M, Deng X, Xiao X, Yin Z, Hu Q, Zhou Z, Zhang F, Zhang R, Wu Y, Sheng W, Zeng Y (2015) Degradable hyaluronic acid/protamine sulfate interpolyelectrolyte complexes as miRNA-delivery nanocapsules for triple-negative breast cancer therapy. Adv Healthc Mater 4:281–290. Google Scholar
  93. Wang Y, Li X, Tao B (2016) Improving classification of mature microRNA by solving class imbalance problem. Sci Rep 6:25941. Google Scholar
  94. Wang Z, Yao Y-J, Zheng F, Guan Z, Zhang L, Dong N, Qin W-J (2017) Mir-138-5p acts as a tumor suppressor by targeting pyruvate dehydrogenase kinase 1 in human retinoblastoma. Eur Rev Med Pharmacol Sci 21:5624–5629Google Scholar
  95. Wecker T, Hoffmeier K, Plötner A, Grüning BA, Horres R, Backofen R, Reinhard T, Schlunck G (2016) MicroRNA profiling in aqueous humor of individual human eyes by next-generation sequencing. Invest Ophthalmol Vis Sci 57:1706–1713. Google Scholar
  96. Wei D, Miao Y, Yu L, Wang D, Wang Y (2018) Downregulation of microRNA-198 suppresses cell proliferation and invasion in retinoblastoma by directly targeting PTEN. Mol Med Rep 18:595–602. Google Scholar
  97. Wu J, Bao J, Kim M, Yuan S, Tang C, Zheng H, Mastick GS, Xu C, Yan W (2014) Two miRNA clusters, miR-34b/c and miR-449, are essential for normal brain development, motile ciliogenesis, and spermatogenesis. Proc Natl Acad Sci USA 111:E2851–E2857. Google Scholar
  98. Wu K, He J, Pu W, Peng Y (2018a) The role of exportin-5 in microRNA biogenesis and cancer. Genom Proteom Bioinf 16:120–126. Google Scholar
  99. Wu S, Ai N, Liu Q, Zhang J (2018b) MicroRNA-448 inhibits the progression of retinoblastoma by directly targeting ROCK1 and regulating PI3K/AKT signalling pathway. Oncol Rep 39:2402–2412. Google Scholar
  100. Wu L, Chen Z, Xing Y (2018c) MiR-506-3p inhibits cell proliferation, induces cell cycle arrest and apoptosis in retinoblastoma by directly targeting NEK6. Cell Biol Int. Google Scholar
  101. Xu X, Jia R, Zhou Y, Song X, Wang J, Qian G, Ge S, Fan X (2011) Microarray-based analysis: identification of hypoxia-regulated microRNAs in retinoblastoma cells. Int J Oncol 38:1385–1393. Google Scholar
  102. Xu X, Ge S, Jia R, Zhou Y, Song X, Zhang H, Fan X (2015) Hypoxia-induced miR-181b enhances angiogenesis of retinoblastoma cells by targeting PDCD10 and GATA6. Oncol Rep 33:2789–2796. Google Scholar
  103. Yang Y, Mei Q (2015) miRNA signature identification of retinoblastoma and the correlations between differentially expressed miRNAs during retinoblastoma progression. Mol Vis 21:1307–1317Google Scholar
  104. Yang G, Fu Y, Zhang L, Lu X, Li Q (2017) miR106b regulates retinoblastoma Y79 cells through Runx3. Oncol Rep 38:3039–3043. Google Scholar
  105. Yang L, Wei N, Wang L, Wang X, Liu Q-H (2018) miR-498 promotes cell proliferation and inhibits cell apoptosis in retinoblastoma by directly targeting CCPG1. Childs Nerv Syst 34:417–422. Google Scholar
  106. Zhang Y, Xue C, Zhu X, Zhu X, Xian H, Huang Z (2016) Suppression of microRNA-125a-5p upregulates the TAZ-EGFR signaling pathway and promotes retinoblastoma proliferation. Cell Signal 28:850–860. Google Scholar
  107. Zhang Y, Zhu X, Zhu X, Wu Y, Liu Y, Yao B, Huang Z (2017) MiR-613 suppresses retinoblastoma cell proliferation, invasion, and tumor formation by targeting E2F5. Tumour Biol 39:1010428317691674. Google Scholar
  108. Zhang J, He J, Zhang L (2018a) The down-regulation of microRNA-137 contributes to the up-regulation of retinoblastoma cell proliferation and invasion by regulating COX-2/PGE2 signaling. Biomed Pharmacother 106:35–42. Google Scholar
  109. Zhang M, Li Q, Pan Y, Wang H, Liu G, Yin H (2018b) MicroRNA-655 attenuates the malignant biological behaviours of retinoblastoma cells by directly targeting PAX6 and suppressing the ERK and p38 MAPK signalling pathways. Oncol Rep 39:2040–2050. Google Scholar
  110. Zhang Y, Wang X, Zhao Y (2018c) MicroRNA-874 prohibits the proliferation and invasion of retinoblastoma cells by directly targeting metadherin. Mol Med Rep. Google Scholar
  111. Zhao J-J, Yang J, Lin J, Yao N, Zhu Y, Zheng J, Xu J, Cheng JQ, Lin J-Y, Ma X (2009) Identification of miRNAs associated with tumorigenesis of retinoblastoma by miRNA microarray analysis. Childs Nerv Syst 25:13–20. Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Ribeirao Preto School of MedicineUniversity of Sao PauloSao PauloBrazil
  2. 2.Anhanguera University of Sao Paulo, UNIANSao PauloBrazil
  3. 3.Faculty of Philosophy, Sciences and Letters at Ribeirao PretoUniversity of Sao PauloSao PauloBrazil

Personalised recommendations