Original Article

Effect of miR‑215 on the Expression of Tumor Suppressor Gene Rb1 in Retinoblastoma Cell Lines


Background: Effect of miR-215 on the expression of tumor suppressor gene retinoblastoma (Rb)1 in Rb cell lines was investigated.

Methods: A total of 128 patients were selected. The expression of miR‑215 in cancer and adjacent healthy tissues of the 128 patients was detected by reverse transcription-quantitative PCR (RT-qPCR). HXO‑Rb44 and Y79 cell lines were transfected with miR‑215 analogs or miR‑215 inhibitors, and the expression of Rb1 protein in the cell lines was detected by western blotting.

Results: The expression of miR-215 in the adjacent healthy tissues of patients was significantly lower than that in cancer tissues (P<0.001). The expression of miR-215 in Y79 and HXO-Rb44 cells was significantly higher than that in APRE-19 cells (P<0.001). The expression of miR-215 in HXO-Rb44 cells was significantly higher than that in Y79 cells (P<0.001). The expression of miR-215 was statistically different from the degree of differentiation and nerve infiltration (P<0.05). The expression of Rb1 in cancer tissues was significantly lower than that in adjacent tissues (P<0.001), the expression of APRE-19 was significantly higher than that in Y79 and HXO-Rb44 cells (P<0.001), and the expression of Rb1 in HXO-Rb44 cells was significantly higher than that in Y79 cells (P<0.05). There was a negative correlation between miR-215 and Rb1 in the tissues of patients, and Rb1 expression decreased with the increase of miR-215 (r=-0.576, P<0.001).

Conclusion: miR‑215 is highly expressed in Rb cell lines, and is related to the clinicopathological features of this disease.

1. Dimaras H, Kimani K, Dimba EA, et al (2012). Retinoblastoma. Lancet, 379: 1436‑1446.
2. de Graaf P, Göricke S, Rodjan F, et al (2012). European Retinoblastoma Imag-ing Collaboration (ERIC): Guidelines for imaging retinoblastoma: Imaging princi-ples and MRI standardization. Pediatr Ra-diol, 42: 2‑14.
3. Broaddus E, Topham A, Singh AD (2009). Incidence of retinoblastoma in the USA: 1975‑2004. Br J Ophthalmol, 93: 21‑23.
4. Lu J, Getz G, Miska EA et al (2005). Mi-cro‑RNA expression profiles classify human cancers. Nature, 435: 834‑838.
5. Georges SA, Biery MC, Kim SY et al (2008). Coordi‑nated regulation of cell cycle transcripts by p53‑inducible microRNAs, miR‑192 and miR‑215. Cancer Res, 68: 10105‑10112.
6. Boni V, Bitarte N, Cristobal I et al (2010). miR‑192/miR‑215 influence 5‑fluorouracil resistance through cell cy-cle‑mediated mech-anisms complemen-tary to its post‑transcriptional thymidilate synthase regulation. Mol Cancer Ther, 9: 2265‑2275.
7. Deng Y, Huang Z, Xu Y, et al (2014). MiR‑215 modulates gastric cancer cell proliferation by targeting RB1. Cancer Lett, 342: 27‑35.
8. Burkhart DL, Sage J (2008). Cellular mecha-nisms of tumour suppression by the reti-noblastoma gene. Nat Rev Cancer, 8: 671‑682.
9. Lee EY, To H, Shew JY, Bookstein R, Scully P, Lee WH (1988). Inactivation of the ret-inoblastoma susceptibility gene in human breast cancers. Science, 241: 218‑221.
10. Gore AJ, Deitz SL, Palam LR, Craven KE, Korc M (2014). Pancreatic can-cer‑associated retinoblastoma 1 dysfunc-tion enables TGF‑β to promote prolifer-ation. J Clin Invest, 124: 338‑352.
11. Feng S, Cong S, Zhang X, et al (2011). Mi-croRNA‑192 targeting retino-blastoma 1 inhibits cell proliferation and induces cell apoptosis in lung cancer cells. Nucleic Ac-ids Res, 39: 6669‑6678.
12. Livak KJ, Schmittgen TD (2001). Analysis of relative gene expression data using re-al‑time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods, 25: 402‑408.
13. Canturk S, Qaddoumi I, Khetan V, et al (2010). Survival of retinoblastoma in less‑developed countries impact of soci-oeconomic and health‑related indicators. Br J Ophthalmol, 94: 1432‑1436.
14. Youn JI, Kumar V, Collazo M et al (2013). Epigenetic silencing of retinoblastoma gene regulates pathologic differentiation of myeloid cells in cancer. Nat Immunol, 14: 211‑220.
15. Sihto H, Kukko H, Koljonen V, Sankila R, Böhling T, Joensuu H (2011). Merkel cell polyomavirus infection, large T antigen, retinoblastoma protein and outcome in Merkel cell carcinoma. Clin Cancer Res, 17: 4806‑4813.
16. Keller A, Leidinger P, Gislefoss R, et al (2011). Stable serum miRNA profiles as potential tool for non‑invasive lung can-cer diagnosis. RNA Biol, 8: 506‑516.
17. White NM, Khella HW, Grigull J, et al (2011). miRNA profiling in metastatic re-nal cell carcinoma reveals a tu-mor‑suppressor effect for miR‑215. Br J Cancer, 105: 1741‑1749.
18. Yang LS, Wang LL, Du QW (2015). Regula-tory effect of Micro­RNA‑215 on the growth of human retinoblastoma cells and the expression of Rb1. Hainan Med J, 26: 3592‑3597 (In Chinese).
19. Wei Y, Sun J, Li X (2017). MicroRNA‑215 enhances invasion and migration by tar-geting retinoblastoma tumor suppressor gene 1 in high‑grade glioma. Biotechnol Lett, 39: 197‑205.
IssueVol 49 No 7 (2020) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijph.v49i7.3583
miR-215; Retinoblastoma; Retinoblastoma (Rb)

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How to Cite
SHAO L, SHENG Z, ZHU Y, LI J, MENG R. Effect of miR‑215 on the Expression of Tumor Suppressor Gene Rb1 in Retinoblastoma Cell Lines. Iran J Public Health. 2020;49(7):1298-1306.