MicroRNA‑466 inhibits osteosarcoma cell proliferation and induces apoptosis by targeting CCND1

Cao,Wei; Fang,Le; Teng,Siyong; Chen,Hongwei; Liu,Tiejun

doi:10.3892/etm.2018.6888

MicroRNA‑466 inhibits osteosarcoma cell proliferation and induces apoptosis by targeting CCND1

Authors:
- Wei Cao
- Le Fang
- Siyong Teng
- Hongwei Chen
- Tiejun Liu
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Affiliations: Clinical Laboratory, Beijing Rehabilitation Hospital of Capital Medical University, Beijing 100041, P.R. China, Department of Blood Transfusion, 521 Hospital of Ordnance Industry, Xi'an, Shaanxi 710065, P.R. China, Department of Cardiovascular Medicine, National Center for Cardiovascular Diseases, Beijing 102300, P.R. China, Clinical Laboratory, Shanghai Songjiang District Central Hospital, Shanghai 201600, P.R. China, Department of Urology, Beijing Rehabilitation Hospital of Capital Medical University, Beijing 100144, P.R. China
Published online on: October 22, 2018 https://doi.org/10.3892/etm.2018.6888
Pages: 5117-5122
Copyright: © Cao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Emerging pieces of evidence indicate that microRNA‑466 (miR‑466) serves as a tumor suppressor in several human tumors, including colorectal cancer and prostate cancer. However, whether miR‑466 is involved in osteosarcoma (OS) progression remains largely unknown. The present study demonstrated that miR‑466 was significantly downregulated in OS tissues and cell lines. Furthermore, it was revealed that the expression of miR‑466 was negatively correlated with OS severity. Moreover, low miR‑466 expression in patients with OS predicted poor prognosis. Through functional experiments, miR‑466 overexpression significantly inhibited the proliferation and cell cycle of OS cells while inducing cellular apoptosis. In terms of mechanism, it was revealed that CCND1 was a target of miR‑466 in OS cells. miR‑466 overexpression suppressed CCND1 expression in OS cells. A reverse association was observed between the expression levels of miR‑466 and CCND1 in OS tissues. Furthermore, CCND1 restoration in OS cells significantly rescued the effects of miR‑466 on cellular proliferation and apoptosis. Overall, the results of the present study demonstrated that miR‑466 suppressed OS progression by targeting CCND1, suggesting that miR‑466 may be a promising biomarker and therapeutic target for OS prognosis and treatment.

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1	Heare T, Hensley MA and Dell'Orfano S: Bone tumors: Osteosarcoma and Ewing's sarcoma. Curr Opin Pediatr. 21:365–372. 2009. View Article : Google Scholar : PubMed/NCBI
2	Shackleton M, Quintana E, Fearon ER and Morrison SJ: Heterogeneity in cancer: Cancer stem cells versus clonal evolution. Cell. 138:822–829. 2009. View Article : Google Scholar : PubMed/NCBI
3	Levings PP, McGarry SV, Currie TP, Nickerson DM, McClellan S, Ghivizzani SC, Steindler DA and Gibbs CP: Expression of an exogenous human Oct-4 promoter identifies tumor-initiating cells in osteosarcoma. Cancer Res. 69:5648–5655. 2009. View Article : Google Scholar : PubMed/NCBI
4	Fagioli F, Aglietta M, Tienghi A, Ferrari S, Brach del Prever A, Vassallo E, Palmero A, Biasin E, Bacci G, Picci P and Madon E: High-dose chemotherapy in the treatment of relapsed osteosarcoma: An Italian sarcoma group study. J Clin Oncol. 20:2150–2156. 2002. View Article : Google Scholar : PubMed/NCBI
5	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
6	Yang Y, Jiang Z, Ma N, Wang B, Liu J, Zhang L and Gu L: MicroRNA-223 targeting STIM1 inhibits the biological behavior of breast cancer. Cell Physiol Biochem. 45:856–866. 2018. View Article : Google Scholar : PubMed/NCBI
7	Zavala-Yoe R, Ramirez-Mendoza RA and Cordero LM: Entropy measures to study and model long term simultaneous evolution of children in Doose and Lennox-Gastaut syndromes. J Integr Neurosci. 15:205–221. 2016. View Article : Google Scholar : PubMed/NCBI
8	Cui Y, Chen LG, Yao HB, Zhang J and Ding KF: Upregulation of microRNA-383 inhibits the proliferation, migration and invasion of colon cancer cells. Oncol Lett. 15:1184–1190. 2018.PubMed/NCBI
9	Du P, Luan X, Liao Y, Mu Y, Yuan Y, Xu J and Zhang J: MicroRNA-509-3p inhibits cell proliferation and invasion via downregulation of X-linked inhibitor of apoptosis in glioma. Oncol Lett. 15:1307–1312. 2018.PubMed/NCBI
10	Wang P, Zhang L, Zhang J and Xu G: MicroRNA-124-3p inhibits cell growth and metastasis in cervical cancer by targeting IGF2BP1. Exp Ther Med. 15:1385–1393. 2018.PubMed/NCBI
11	Wang H, Xing D, Ren D, Feng W, Chen Y, Zhao Z, Xiao Z and Peng Z: MicroRNA-643 regulates the expression of ZEB1 and inhibits tumorigenesis in osteosarcoma. Mol Med Rep. 16:5157–5164. 2017. View Article : Google Scholar : PubMed/NCBI
12	Zhou Z, Li Z, Shen Y and Chen T: MicroRNA-138 directly targets TNFAIP8 and acts as a tumor suppressor in osteosarcoma. Exp Ther Med. 14:3665–3673. 2017. View Article : Google Scholar : PubMed/NCBI
13	Lin T, Ma Q, Zhang Y, Zhang H, Yan J and Gao C: MicroRNA-27a functions as an oncogene in human osteosarcoma by targeting CCNG1. Oncol Lett. 15:1067–1071. 2018.PubMed/NCBI
14	Colden M, Dar AA, Saini S, Dahiya PV, Shahryari V, Yamamura S, Tanaka Y, Stein G, Dahiya R and Majid S: MicroRNA-466 inhibits tumor growth and bone metastasis in prostate cancer by direct regulation of osteogenic transcription factor RUNX2. Cell Death Dis. 8:e25722017. View Article : Google Scholar : PubMed/NCBI
15	Tong F, Ying Y, Pan H, Zhao W, Li H and Zhan X: MicroRNA-466 (miR-466) functions as a tumor suppressor and prognostic factor in colorectal cancer (CRC). Bosn J Basic Med Sci. Jan 17–2018.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI
16	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
17	Huang Y, Shen XJ, Zou Q, Wang SP, Tang SM and Zhang GZ: Biological functions of microRNAs: A review. J Physiol Biochem. 67:129–139. 2011. View Article : Google Scholar : PubMed/NCBI
18	Wang ZM, Wan XH, Sang GY, Zhao JD, Zhu QY and Wang DM: miR-15a-5p suppresses endometrial cancer cell growth via Wnt/β-catenin signaling pathway by inhibiting WNT3A. Eur Rev Med Pharmacol Sci. 21:4810–4818. 2017.PubMed/NCBI
19	Nugent M: microRNA and bone cancer. Adv Exp Med Biol. 889:201–230. 2015. View Article : Google Scholar : PubMed/NCBI
20	Gao X, Han D and Fan W: Down-regulation of RBP-J mediated by microRNA-133a suppresses dendritic cells and functions as a potential tumor suppressor in osteosarcoma. Exp Cell Res. 349:264–272. 2016. View Article : Google Scholar : PubMed/NCBI
21	Sun P, Shen Y, Gong JM, Zhou LL, Sheng JH and Duan FJ: A new MicroRNA expression signature for cervical cancer. Int J Gynecol Cancer. 27:339–343. 2017. View Article : Google Scholar : PubMed/NCBI
22	Zhao M, Xu P, Liu Z, Zhen Y, Chen Y, Liu Y, Fu Q, Deng X, Liang Z, Li Y, et al: Dual roles of miR-374a by modulated c-Jun respectively targets CCND1-inducing PI3K/AKT signal and PTEN-suppressing Wnt/β-catenin signaling in non-small-cell lung cancer. Cell Death Dis. 9:782018. View Article : Google Scholar : PubMed/NCBI
23	Huang H, Han Y, Yang X, Li M, Zhu R, Hu J, Zhang X, Wei R, Li K and Gao R: HNRNPK inhibits gastric cancer cell proliferation through p53/p21/CCND1 pathway. Oncotarget. 8:103364–103374. 2017. View Article : Google Scholar : PubMed/NCBI
24	Chen DG, Zhu B, Lv SQ, Zhu H, Tang J, Huang C, Li Q, Zhou P, Wang DL and Li GH: Inhibition of EGR1 inhibits glioma proliferation by targeting CCND1 promoter. J Exp Clin Cancer Res. 36:1862017. View Article : Google Scholar : PubMed/NCBI
25	Xue J, Qin Z, Li X, Zhang J, Zheng Y, Xu W, Cao Q and Wang Z: Genetic polymorphisms in cyclin D1 are associated with risk of renal cell cancer in the Chinese population. Oncotarget. 8:80889–80899. 2017. View Article : Google Scholar : PubMed/NCBI
26	Yao Y, Luo J, Sun Q, Xu T, Sun S, Chen M, Lin X, Qian Q, Zhang Y, Cao L, et al: HOXC13 promotes proliferation of lung adenocarcinoma via modulation of CCND1 and CCNE1. Am J Cancer Res. 7:1820–1834. 2017.PubMed/NCBI
27	Wu J, Cui LL, Yuan J, Wang Y and Song S: Clinical significance of the phosphorylation of MAPK and protein expression of cyclin D1 in human osteosarcoma tissues. Mol Med Rep. 15:2303–2307. 2017. View Article : Google Scholar : PubMed/NCBI
28	Li Z, Wang C, Prendergast GC and Pestell RG: Cyclin D1 functions in cell migration. Cell Cycle. 5:2440–2442. 2006. View Article : Google Scholar : PubMed/NCBI
29	Fu M, Rao M, Bouras T, Wang C, Wu K, Zhang X, Li Z, Yao TP and Pestell RG: Cyclin D1 inhibits peroxisome proliferator-activated receptor gamma-mediated adipogenesis through histone deacetylase recruitment. J Biol Chem. 280:16934–16941. 2005. View Article : Google Scholar : PubMed/NCBI