MicroRNA‑655 suppresses cell proliferation and invasion in oral squamous cell carcinoma by directly targeting metadherin and regulating the PTEN/AKT pathway Retraction in /10.3892/mmr.2022.12897

Wang,Qiang; Lv,Longkun; Li,Yuan; Ji,Honghai

doi:10.3892/mmr.2018.9292

MicroRNA‑655 suppresses cell proliferation and invasion in oral squamous cell carcinoma by directly targeting metadherin and regulating the PTEN/AKT pathway

Retraction in: /10.3892/mmr.2022.12897

Authors:
- Qiang Wang
- Longkun Lv
- Yuan Li
- Honghai Ji
View Affiliations

Affiliations: Department of Stomatology, Yidu Central Hospital of Weifang, Weifang, Shandong 262500, P.R. China, Department of Clinical Medicine, Weifang Medical University, Weifang, Shandong 261053, P.R. China
Published online on: July 16, 2018 https://doi.org/10.3892/mmr.2018.9292
Pages: 3106-3114

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

MicroRNAs (miRNAs) are important regulators of a variety of biological processes and their dysregulation is closely related to cancer formation and progression. Therefore, examination of aberrantly expressed miRNAs in oral squamous cell carcinoma (OSCC) may provide important clues for the diagnosis and treatment of patients with OSCC. The aim of the present study was to determine miRNA (miR)‑655‑3p expression in OSCC tissues and cell lines, and to investigate the biological roles and mechanisms of miR‑655‑3p associated with OSCC. Data from the present study indicated that miR‑655 expression was significantly downregulated in human OSCC tissues and cell lines. Overexpression of miR‑655 attenuated cell proliferation and invasion in OSCC in vitro. Metadherin (MTDH) mRNA was predicted as a potential target of miR‑655 by bioinformatics analysis, and this was confirmed by luciferase reporter assay, reverse transcription‑quantitative polymerase chain reaction and western blot analysis. In OSCC tissues, MTDH was highly expressed and inversely correlated with miR‑655 expression levels. MTDH overexpression reversed the inhibitory effects of miR‑655 mimics in OSCC cells. Notably, the upregulation of miR‑655 expression inhibited the activation of the phosphatase and tensin homolog (PTEN)/RAC‑α serine/threonine‑protein kinase (AKT) pathway in OSCC cells. Therefore, these results may provide the first evidence that miR‑655 targets MTDH to inhibit proliferation and invasion of OSCC by inhibiting PTEN/AKT signaling. Thus, the restoration of miR‑655 expression may be a novel therapeutic strategy for patients with OSCC.

View Figures

View References

1	Min A, Zhu C, Peng S, Rajthala S, Costea DE and Sapkota D: MicroRNAs as important players and biomarkers in oral carcinogenesis. Biomed Res Int. 2015:1869042015. View Article : Google Scholar : PubMed/NCBI
2	Warnakulasuriya S: Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 45:309–316. 2009. View Article : Google Scholar : PubMed/NCBI
3	Zaravinos A: An updated overview of HPV-associated head and neck carcinomas. Oncotarget. 5:3956–3969. 2014. View Article : Google Scholar : PubMed/NCBI
4	Leemans CR, Braakhuis BJ and Brakenhoff RH: The molecular biology of head and neck cancer. Nat Rev Cancer. 11:9–22. 2011. View Article : Google Scholar : PubMed/NCBI
5	Perez-Sayans M, Suarez-Penaranda JM, Padin-Iruegas ME, Gayoso-Diz P, Reis-De Almeida M, Barros-Angueira F, Gandara-Vila P, Blanco-Carrion A and Garcia-Garcia A: The loss of p16 expression worsens the prognosis of OSCC. Appl Immunohistochem Mol Morphol. 23:724–732. 2015. View Article : Google Scholar : PubMed/NCBI
6	Liang L, Zhang T, Kong Q, Liang J and Liao G: A meta-analysis on selective versus comprehensive neck dissection in oral squamous cell carcinoma patients with clinically node-positive neck. Oral Oncol. 51:1076–1081. 2015. View Article : Google Scholar : PubMed/NCBI
7	Moreno-Moya JM, Vilella F and Simon C: MicroRNA: Key gene expression regulators. Fertil Steril. 101:1516–1523. 2014. View Article : Google Scholar : PubMed/NCBI
8	John B, Enright AJ, Aravin A, Tuschl T, Sander C and Marks DS: Human MicroRNA targets. PLoS Biol. 2:e3632004. View Article : Google Scholar : PubMed/NCBI
9	Vasudevan S, Tong Y and Steitz JA: Switching from repression to activation: microRNAs can up-regulate translation. Science. 318:1931–1934. 2007. View Article : Google Scholar : PubMed/NCBI
10	Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI
11	Wang YJ, Zhang ZF, Fan SH, Zhuang J, Shan Q, Han XR, Wen X, Li MQ, Hu B, Sun CH, et al: MicroRNA-433 inhibits oral squamous cell carcinoma cells by targeting FAK. Oncotarget. 8:100227–100241. 2017.PubMed/NCBI
12	Yang D, Du G, Xu A, Xi X and Li D: Expression of miR-149-3p inhibits proliferation, migration and invasion of bladder cancer by targeting S100A4. Am J Cancer Res. 7:2209–2219. 2017.PubMed/NCBI
13	Zabaglia LM, Bartolomeu NC, Dos Santos MP, Peruquetti RL, Chen E, de Arruda Cardoso, Smith M, Payao SLM and Rasmussen LT: Decreased MicroRNA miR-181c expression associated with gastric cancer. J Gastrointest Cancer. 49:97–101. 2018. View Article : Google Scholar : PubMed/NCBI
14	Celano M, Rosignolo F, Maggisano V, Pecce V, Iannone M, Russo D and Bulotta S: MicroRNAs as biomarkers in thyroid carcinoma. Int J Genomics. 2017:64965702017. View Article : Google Scholar : PubMed/NCBI
15	Kang M, Shi J, Peng N and He S: MicroRNA-211 promotes non-small-cell lung cancer proliferation and invasion by targeting MxA. Onco Targets Ther. 10:5667–5675. 2017. View Article : Google Scholar : PubMed/NCBI
16	Tavazoie SF, Alarcon C, Oskarsson T, Padua D, Wang Q, Bos PD, Gerald WL and Massague J: Endogenous human microRNAs that suppress breast cancer metastasis. Nature. 451:147–152. 2008. View Article : Google Scholar : PubMed/NCBI
17	Cui F, Li X, Zhu X, Huang L, Huang Y, Mao C, Yan Q, Zhu J, Zhao W and Shi H: MiR-125b inhibits tumor growth and promotes apoptosis of cervical cancer cells by targeting phosphoinositide 3-kinase catalytic subunit delta. Cell Physiol Biochem. 30:1310–1318. 2012. View Article : Google Scholar : PubMed/NCBI
18	Zuo QF, Zhang R, Li BS, Zhao YL, Zhuang Y, Yu T, Gong L, Li S, Xiao B and Zou QM: MicroRNA-141 inhibits tumor growth and metastasis in gastric cancer by directly targeting transcriptional co-activator with PDZ-binding motif, TAZ. Cell Death Dis. 6:e16232015. View Article : Google Scholar : PubMed/NCBI
19	Zhao XQ, Liang B, Jiang K and Zhang HY: Down-regulation of miR-655-3p predicts worse clinical outcome in patients suffering from hepatocellular carcinoma. Eur Rev Med Pharmacol Sci. 21:748–752. 2017.PubMed/NCBI
20	Wu G, Zheng K, Xia S, Wang Y, Meng X, Qin X and Cheng Y: MicroRNA-655-3p functions as a tumor suppressor by regulating ADAM10 and β-catenin pathway in hepatocellular carcinoma. J Exp Clin Cancer Res. 35:892016. View Article : Google Scholar : PubMed/NCBI
21	Lv ZD, Kong B, Liu XP, Jin LY, Dong Q, Li FN and Wang HB: miR-655 suppresses epithelial-to-mesenchymal transition by targeting Prrx1 in triple-negative breast cancer. J Cell Mol Med. 20:864–873. 2016. View Article : Google Scholar : PubMed/NCBI
22	Wang Y, Zang W, Du Y, Ma Y, Li M, Li P, Chen X, Wang T, Dong Z and Zhao G: Mir-655 up-regulation suppresses cell invasion by targeting pituitary tumor-transforming gene-1 in esophageal squamous cell carcinoma. J Transl Med. 11:3012013. View Article : Google Scholar : PubMed/NCBI
23	Li J, Li C, Li H, Zhang T, Hao X, Chang J and Xu Y: MicroRNA30a5p suppresses tumor cell proliferation of human renal cancer via the MTDH/PTEN/AKT pathway. Int J Mol Med. 41:1021–1029. 2018.PubMed/NCBI
24	Li L and Zhang H: MicroRNA-379 inhibits cell proliferation and invasion in glioma via targeting metadherin and regulating PTEN/AKT pathway. Mol Med Rep. 17:4049–4056. 2018.PubMed/NCBI
25	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
26	Xia X, Du R, Zhao L, Sun W and Wang X: Expression of AEG-1 and microvessel density correlates with metastasis and prognosis of oral squamous cell carcinoma. Hum Pathol. 45:858–865. 2014. View Article : Google Scholar : PubMed/NCBI
27	Seyedmajidi M, Sohanian S, Abbaszadeh H, Moslemi D and Bijani A: Astrocyte elevated gene 1 (AEG-1): A promising candidate for molecular targeted therapy in oral squamous cell carcinomas. Asian Pac J Cancer Prev. 18:3301–3305. 2017.PubMed/NCBI
28	Wang Y, Wang T, Sun Y, Sun W and Wang X: Astrocyte elevated gene-1 promotes tumour growth and invasion by inducing EMT in oral squamous cell carcinoma. Sci Rep. 7:154472017. View Article : Google Scholar : PubMed/NCBI
29	Wang YP, Liu IJ, Chiang CP and Wu HC: Astrocyte elevated gene-1 is associated with metastasis in head and neck squamous cell carcinoma through p65 phosphorylation and upregulation of MMP1. Mol Cancer. 12:1092013. View Article : Google Scholar : PubMed/NCBI
30	Garzon R, Calin GA and Croce CM: MicroRNAs in Cancer. Annu Rev Med. 60:167–179. 2009. View Article : Google Scholar : PubMed/NCBI
31	Garzon R and Marcucci G: Potential of microRNAs for cancer diagnostics, prognostication and therapy. Curr Opin Oncol. 24:655–659. 2012. View Article : Google Scholar : PubMed/NCBI
32	Schickel R, Boyerinas B, Park SM and Peter ME: MicroRNAs: Key players in the immune system, differentiation, tumorigenesis and cell death. Oncogene. 27:5959–5974. 2008. View Article : Google Scholar : PubMed/NCBI
33	Liang HQ, Wang RJ, Diao CF, Li JW, Su JL and Zhang S: The PTTG1-targeting miRNAs miR-329, miR-300, miR-381 and miR-655 inhibit pituitary tumor cell tumorigenesis and are involved in a p53/PTTG1 regulation feedback loop. Oncotarget. 6:29413–29427. 2015. View Article : Google Scholar : PubMed/NCBI
34	Kitamura K, Seike M, Okano T, Matsuda K, Miyanaga A, Mizutani H, Noro R, Minegishi Y, Kubota K and Gemma A: MiR-134/487b/655 cluster regulates TGF-beta-induced epithelial-mesenchymal transition and drug resistance to gefitinib by targeting MAGI2 in lung adenocarcinoma cells. Mol Cancer Ther. 13:444–453. 2014. View Article : Google Scholar : PubMed/NCBI
35	Su ZZ, Kang DC, Chen Y, Pekarskaya O, Chao W, Volsky DJ and Fisher PB: Identification and cloning of human astrocyte genes displaying elevated expression after infection with HIV-1 or exposure to HIV-1 envelope glycoprotein by rapid subtraction hybridization, RaSH. Oncogene. 21:3592–3602. 2002. View Article : Google Scholar : PubMed/NCBI
36	He Z, He M, Wang C, Xu B, Tong L, He J, Sun B, Wei L and Chu M: Prognostic significance of astrocyte elevated gene-1 in human astrocytomas. Int J Clin Exp Pathol. 7:5038–5044. 2014.PubMed/NCBI
37	Li J, Zhang N, Song LB, Liao WT, Jiang LL, Gong LY, Wu J, Yuan J, Zhang HZ, Zeng MS and Li M: Astrocyte elevated gene-1 is a novel prognostic marker for breast cancer progression and overall patient survival. Clin Cancer Res. 14:3319–3326. 2008. View Article : Google Scholar : PubMed/NCBI
38	Dong L, Qin S, Li Y, Zhao L, Dong S, Wang Y, Zhang C and Han S: High expression of astrocyte elevated gene-1 is associated with clinical staging, metastasis and unfavorable prognosis in gastric carcinoma. Tumour Biol. 36:2169–2178. 2015. View Article : Google Scholar : PubMed/NCBI
39	Nikpour M, Emadi-Baygi M, Fischer U, Niegisch G, Schulz WA and Nikpour P: MTDH/AEG-1 contributes to central features of the neoplastic phenotype in bladder cancer. Urol Oncol. 32:670–677. 2014. View Article : Google Scholar : PubMed/NCBI
40	Yu JQ, Zhou Q, Zhu H, Zheng FY and Chen ZW: Overexpression of astrocyte elevated gene-1 (AEG-1) in cervical cancer and its correlation with angiogenesis. Asian Pac J Cancer Prev. 16:2277–2281. 2015. View Article : Google Scholar : PubMed/NCBI
41	Alyasiri NS, Mehdi SJ, Alam MS, Ali A, Mandal AK, Gupta S, Singh I and Rizvi MM: PTEN-mediated AKT activation contributes to the reduced apoptosis among Indian oral squamous cell carcinoma patients. J Cancer Res Clin Oncol. 138:103–109. 2012. View Article : Google Scholar : PubMed/NCBI
42	Gan YH and Zhang S: PTEN/AKT pathway involved in histone deacetylases inhibitor induced cell growth inhibition and apoptosis of oral squamous cell carcinoma cells. Oral Oncol. 45:e150–e154. 2009. View Article : Google Scholar : PubMed/NCBI