miR‑494 promotes progression of retinoblastoma via PTEN through PI3K/AKT signaling pathway

Xu,Fen; Liu,Guiqin; Wang,Lijuan; Wang,Xiyan; Jin,Xiao; Bo,Wen

doi:10.3892/ol.2020.11749

miR‑494 promotes progression of retinoblastoma via PTEN through PI3K/AKT signaling pathway

Authors:
- Fen Xu
- Guiqin Liu
- Lijuan Wang
- Xiyan Wang
- Xiao Jin
- Wen Bo
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Affiliations: Department of Clinical Laboratory, Jinan Zhangqiu District Hospital of TCM, Jinan, Shandong 250200, P.R. China, Department of Ophthalmology, Jinan Zhangqiu District Hospital of TCM, Jinan, Shandong 250200, P.R. China, Department of Paediatrics, The People's Hospital of Zhangqiu Area, Jinan, Shandong 250200, P.R. China, Department of Anesthesiology, The People's Hospital of Zhangqiu Area, Jinan, Shandong 250200, P.R. China, Department of Rehabilitation Medicine, The People's Hospital of Zhangqiu Area, Jinan, Shandong 250200, P.R. China, Department of Ophthalmology, Maternity and Child Health Care of Zaozhuang, Zaozhuang Ophthalmological Hospital, Zaozhuang, Shandong 277100, P.R. China
Published online on: June 17, 2020 https://doi.org/10.3892/ol.2020.11749
Pages: 1952-1960
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Increasing evidence has indicated that the dysregulation of microRNA (miRNA) occur in the pathogenesis of retinoblastoma (RB). Aim of the present study was to investigate the possible role of miR‑494 (miR‑494‑3p) in RB. It was demonstrated that miR‑494 expression was increased in RB tissue samples and cell lines. Also, it was prominently associated with clinicopathological features. Functional assays showed that RB cell proliferation, invasion and migration can be promoted by miR‑494 overexpression. Besides, phosphatase and tensin homolog (PTEN) was verified as a possible target of miR‑494 by a luciferase assay, western blot and qRT‑PCR assay in RB. miR‑494 and PTEN expression was negatively related in a correlation analysis on tumor tissues of 66 patients. In addition, PTEN was proved to reverse miR‑494 effect on RB cell progression. Moreover, PI3K/AKT signaling pathway was validated to take part in RB progression. Taken together, the current study proposes that miR‑494 might function as a tumor promoter and regulates RB progression through targeting PTEN.

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1	Dimaras H, Dimba EA and Gallie BL: Challenging the global retinoblastoma survival disparity through a collaborative research effort. Br J Ophthalmol. 94:1415–1416. 2010. View Article : Google Scholar : PubMed/NCBI
2	Kivelä T: The epidemiological challenge of the most frequent eye cancer: Retinoblastoma, an issue of birth and death. Br J Ophthalmol. 93:1129–1131. 2009. View Article : Google Scholar : PubMed/NCBI
3	Narang S, Mashayekhi A, Rudich D and Shields CL: Predictors of long-term visual outcome after chemoreduction for management of intraocular retinoblastoma. Clin Exp Ophthalmol. 40:736–742. 2012. View Article : Google Scholar : PubMed/NCBI
4	Shinohara ET, DeWees T and Perkins SM: Subsequent malignancies and their effect on survival in patients with retinoblastoma. Pediatr Blood Cancer. 61:116–119. 2014. View Article : Google Scholar : PubMed/NCBI
5	Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, et al European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group, : Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 352:987–996. 2005. View Article : Google Scholar : PubMed/NCBI
6	Holland EC: Gliomagenesis: Genetic alterations and mouse models. Nat Rev Genet. 2:120–129. 2001. View Article : Google Scholar : PubMed/NCBI
7	Liu S, Hu C, Wang Y, Shi G, Li Y and Wu H: miR-124 inhibits proliferation and invasion of human retinoblastoma cells by targeting STAT3. Oncol Rep. 36:2398–2404. 2016. View Article : Google Scholar : PubMed/NCBI
8	Wang L, Lyu X, Ma Y, Wu F and Wang L: MicroRNA 504 targets AEG 1 and inhibits cell proliferation and invasion in retinoblastoma. Mol Med Rep. 19:2935–2942. 2019.PubMed/NCBI
9	Guo L, Bai Y, Ji S and Ma H: MicroRNA 98 suppresses cell growth and invasion of retinoblastoma via targeting the IGF1R/k Ras/Raf/MEK/ERK signaling pathway. Int J Oncol. 54:807–820. 2019.PubMed/NCBI
10	Golabchi K, Soleimani-Jelodar R, Aghadoost N, Momeni F, Moridikia A, Nahand JS, Masoudifar A, Razmjoo H and Mirzaei H: MicroRNAs in retinoblastoma: Potential diagnostic and therapeutic biomarkers. J Cell Physiol. 233:3016–3023. 2018. View Article : Google Scholar : PubMed/NCBI
11	Yu F, Pang G and Zhao G: ANRIL acts as onco-lncRNA by regulation of microRNA-24/c-Myc, MEK/ERK and Wnt/β-catenin pathway in retinoblastoma. Int J Biol Macromol. 128:583–592. 2019. View Article : Google Scholar : PubMed/NCBI
12	Sun Z, Zhang A and Zhang L: Inhibition of microRNA 492 attenuates cell proliferation and invasion in retinoblastoma via directly targeting LATS2. Mol Med Rep. 19:1965–1971. 2019.PubMed/NCBI
13	Wang J, Wang X, Li Z, Liu H and Teng Y: MicroRNA-183 suppresses retinoblastoma cell growth, invasion and migration by targeting LRP6. FEBS J. 281:1355–1365. 2014. View Article : Google Scholar : PubMed/NCBI
14	Dalgard CL, Gonzalez M, deNiro JE and O'Brien JM: Differential microRNA-34a expression and tumor suppressor function in retinoblastoma cells. Invest Ophthalmol Vis Sci. 50:4542–4551. 2009. View Article : Google Scholar : PubMed/NCBI
15	Zhao JJ, Yang J, Lin J, Yao N, Zhu Y, Zheng J, Xu J, Cheng JQ, Lin JY and Ma X: Identification of miRNAs associated with tumorigenesis of retinoblastoma by miRNA microarray analysis. Childs Nerv Syst. 25:13–20. 2009. View Article : Google Scholar : PubMed/NCBI
16	Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, et al: PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 275:1943–1947. 1997. View Article : Google Scholar : PubMed/NCBI
17	Tay Y, Kats L, Salmena L, Weiss D, Tan SM, Ala U, Karreth F, Poliseno L, Provero P, Di Cunto F, et al: Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs. Cell. 147:344–357. 2011. View Article : Google Scholar : PubMed/NCBI
18	Xu W, Yang Z, Zhou SF and Lu N: Posttranslational regulation of phosphatase and tensin homolog (PTEN) and its functional impact on cancer behaviors. Drug Des Devel Ther. 8:1745–1751. 2014. View Article : Google Scholar : PubMed/NCBI
19	Wu W, Yang J, Feng X, Wang H, Ye S, Yang P, Tan W, Wei G and Zhou Y: MicroRNA-32 (miR-32) regulates phosphatase and tensin homologue (PTEN) expression and promotes growth, migration, and invasion in colorectal carcinoma cells. Mol Cancer. 12:302013. View Article : Google Scholar : PubMed/NCBI
20	Wang ZX, Lu BB, Wang H, Cheng ZX and Yin YM: MicroRNA-21 modulates chemosensitivity of breast cancer cells to doxorubicin by targeting PTEN. Arch Med Res. 42:281–290. 2011. View Article : Google Scholar : PubMed/NCBI
21	Ma F, Zhang J, Zhong L, Wang L, Liu Y, Wang Y, Peng L and Guo B: Upregulated microRNA-301a in breast cancer promotes tumor metastasis by targeting PTEN and activating Wnt/β-catenin signaling. Gene. 535:191–197. 2014. View Article : Google Scholar : PubMed/NCBI
22	Rong D, Lu C, Zhang B, Fu K, Zhao S, Tang W and Cao H: CircPSMC3 suppresses the proliferation and metastasis of gastric cancer by acting as a competitive endogenous RNA through sponging miR-296-5p. Mol Cancer. 18:252019. View Article : Google Scholar : PubMed/NCBI
23	Akgun S, Kucuksayan H, Ozes ON, Can O, Alikanoglu AS, Yildiz M and Akca H: NF-κB-induced upregulation of miR-548as-3p increases invasion of NSCLC by targeting PTEN. Anticancer Agents Med Chem. 19:1058–1068. 2019. View Article : Google Scholar : PubMed/NCBI
24	Zhao YS, Yang WC, Xin HW, Han JX and Ma SG: MiR-182-5p knockdown targeting PTEN inhibits cell proliferation and invasion of breast cancer cells. Yonsei Med J. 60:148–157. 2019. View Article : Google Scholar : PubMed/NCBI
25	Zhu L, Wang X, Wang T, Zhu W and Zhou X: miR-494-3p promotes the progression of endometrial cancer by regulating the PTEN/PI3K/AKT pathway. Mol Med Rep. 19:581–588. 2019.PubMed/NCBI
26	Zhang Q, Li Y, Zhao M, Lin H, Wang W, Li D, Cui W, Zhou C, Zhong J and Huang C: MiR-494 acts as a tumor promoter by targeting CASP2 in non-small cell lung cancer. Sci Rep. 9:30082019. View Article : Google Scholar : PubMed/NCBI
27	He H, Liao X, Yang Q, Liu Y, Peng Y, Zhong H, Yang J, Zhang H, Yu Z, Zuo Y, et al: MicroRNA-494-3p promotes cell growth, migration, and invasion of nasopharyngeal carcinoma by targeting Sox7. Technol Cancer Res Treat. Jan 1–2018.(Epub ahead of print). doi: 10.1177/1533033818809993. View Article : Google Scholar
28	Shen Z, Li Y, Zhao C, Wang F, Zhou R and Chen G: miR-494 BAG 1 axis is involved in cinobufacini induced cell proliferation and apoptosis in gastric cancer. Mol Med Rep. 17:7435–7441. 2018.PubMed/NCBI
29	Cheng L, Kong B, Zhao Y and Jiang J: miR-494 inhibits cervical cancer cell proliferation through upregulation of SOCS6 expression. Oncol Lett. 15:3075–3080. 2018.PubMed/NCBI
30	Zhang Y, Guo L, Li Y, Feng GH, Teng F, Li W and Zhou Q: MicroRNA-494 promotes cancer progression and targets adenomatous polyposis coli in colorectal cancer. Mol Cancer. 17:12018. View Article : Google Scholar : PubMed/NCBI
31	Lee YR, Chen M and Pandolfi PP: The functions and regulation of the PTEN tumour suppressor: New modes and prospects. Nat Rev Mol Cell Biol. 19:547–562. 2018. View Article : Google Scholar : PubMed/NCBI
32	Schroeder C, Grell J, Hube-Magg C, Kluth M, Lang D, Simon R, Höflmayer D, Minner S, Burandt E, Clauditz TS, et al: Aberrant expression of the microtubule-associated protein tau is an independent prognostic feature in prostate cancer. BMC Cancer. 19:1932019. View Article : Google Scholar : PubMed/NCBI
33	Kim TH, Park JH and Woo JS: Resveratrol induces cell death through ROS dependent downregulation of Notch1/PTEN/Akt signaling in ovarian cancer cells. Mol Med Rep. 19:3353–3360. 2019.PubMed/NCBI
34	Cao Y, Xia F, Wang P and Gao M: MicroRNA 93-5p promotes the progression of human retinoblastoma by regulating the PTEN/PI3K/AKT signaling pathway. Mol Med Rep. 18:5807–5814. 2018.PubMed/NCBI
35	Wei D, Miao Y, Yu L, Wang D and Wang Y: Downregulation of microRNA-198 suppresses cell proliferation and invasion in retinoblastoma by directly targeting PTEN. Mol Med Rep. 18:595–602. 2018.PubMed/NCBI
36	Lin A, Piao HL, Zhuang L, Sarbassov D, Ma L and Gan B: FoxO transcription factors promote AKT Ser473 phosphorylation and renal tumor growth in response to pharmacologic inhibition of the PI3K-AKT pathway. Cancer Res. 74:1682–1693. 2014. View Article : Google Scholar : PubMed/NCBI
37	Spangle JM, Roberts TM and Zhao JJ: The emerging role of PI3K/AKT-mediated epigenetic regulation in cancer. Biochim Biophys Acta Rev Cancer. 1868:123–131. 2017. View Article : Google Scholar : PubMed/NCBI
38	Xie C, Lu H, Nomura A, Hanse EA, Forster CL, Parker JB, Linden MA, Karasch C and Hallstrom TC: Co-deleting Pten with Rb in retinal progenitor cells in mice results in fully penetrant bilateral retinoblastomas. Mol Cancer. 14:932015. View Article : Google Scholar : PubMed/NCBI
39	Kim BR, Ha J, Lee S, Park J and Cho S: Anti-cancer effects of ethanol extract of Reynoutria japonica Houtt. radix in human hepatocellular carcinoma cells via inhibition of MAPK and PI3K/Akt signaling pathways. J Ethnopharmacol. 245:1121792019. View Article : Google Scholar : PubMed/NCBI
40	Haddadi N, Lin Y, Travis G, Simpson AM, Nassif NT and McGowan EM: PTEN/PTENP1: ‘Regulating the regulator of RTK-dependent PI3K/Akt signalling’, new targets for cancer therapy. Mol Cancer. 17:372018. View Article : Google Scholar : PubMed/NCBI
41	Fu X, Wen H, Jing L, Yang Y, Wang W, Liang X, Nan K, Yao Y and Tian T: MicroRNA-155-5p promotes hepatocellular carcinoma progression by suppressing PTEN through the PI3K/Akt pathway. Cancer Sci. 108:620–631. 2017. View Article : Google Scholar : PubMed/NCBI