miR-202-5p inhibits the migration and invasion of osteosarcoma cells by targeting ROCK1

Li,Congda; Ma,Deying; Yang,Jinhu; Lin,Xiangbo; Chen,Bo

doi:10.3892/ol.2018.8694

miR-202-5p inhibits the migration and invasion of osteosarcoma cells by targeting ROCK1

Authors:
- Congda Li
- Deying Ma
- Jinhu Yang
- Xiangbo Lin
- Bo Chen
View Affiliations

Affiliations: Department of Orthopedic, People's Hospital of Rizhao, Rizhao, Shandong 276800, P.R. China, Department of Orthopedic, People's Hospital of Rizhao, Rizhao, Shandong 276800, P.R. China
Published online on: May 10, 2018 https://doi.org/10.3892/ol.2018.8694
Pages: 829-834
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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

Many studies have shown that microRNA regulates the development and treatment of osteosarcoma (OS). In many human cancer studies, the expression of microRNA‑202 has been shown to be abnormal. The aim of the study was to examine the role of miR‑202‑5p in the occurrence and formation of OS. miR‑202‑5p and Rho‑associated coiled‑coil containing protein kinase 1 (ROCK1) levels were assessed using RT‑qPCR in OS tissues and cell lines. The cell migrating and invasive abilities were detected by the Transwell assay in OS. Moreover, the relationship between miR‑202‑5p and ROCK1 was verified via luciferase reporter assay. The protein level of ROCK1 was identified by western blot analysis. Downregulation of miR‑202‑5p was identified in OS tissues and cell lines. In addition, the miR‑202‑5p overexpression had inhibitory action for cell migration and invasion in OS. Moreover, miR‑202‑5p directly targeted ROCK1 and negatively regulated its expression. Upregulation of ROCK1 had a carcinogenic effect in OS. Furthermore, the upregulation of ROCK1 restored the suppressive effect of miR‑202‑5p. miR‑202‑5p, in turn, weakened the abilities of cell migration and invasion in OS by inhibiting ROCK1 expression. As a result, miR‑202‑5p may be developed as a potential pathway in the reatment of OS.

View Figures

View References

1	Mirabello L, Troisi RJ and Savage SA: Osteosarcoma incidence and survival rates from 1973 to 2004: Data from the Surveillance, Epidemiology, and End Results Program. Cancer. 115:1531–1543. 2009. View Article : Google Scholar : PubMed/NCBI
2	Allison DC, Carney SC, Ahlmann ER, Hendifar A, Chawla S, Fedenko A, Angeles C and Menendez LR: A meta-analysis of osteosarcoma outcomes in the modern medical era. Sarcoma. 2012:7048722012. View Article : Google Scholar : PubMed/NCBI
3	Ottaviani G and Jaffe N: The epidemiology of osteosarcoma. Cancer Treat Res. 152:3–13. 2009. View Article : Google Scholar : PubMed/NCBI
4	Lee JA, Kim DH, Lim JS, Park KD, Song WS, Lee SY and Jeon DG: The survival of osteosarcoma patients 10 years old or younger is not worse than the survival of older patients: A retrospective analysis. Cancer Res Treat. 39:160–164. 2007. View Article : Google Scholar : PubMed/NCBI
5	Asangani IA, Rasheed SA, Nikolova DA, Leupold JH, Colburn NH, Post S and Allgayer H: MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene. 27:2128–2136. 2008. View Article : Google Scholar : PubMed/NCBI
6	Liu B, Peng XC, Zheng XL, Wang J and Qin YW: MiR-126 restoration down-regulate VEGF and inhibit the growth of lung cancer cell lines in vitro and in vivo. Lung Cancer. 66:169–175. 2009. View Article : Google Scholar : PubMed/NCBI
7	Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, Taccioli C, Volinia S, Liu CG, Alder H, et al: MicroRNA signatures in human ovarian cancer. Cancer Res. 67:8699–8707. 2007. View Article : Google Scholar : PubMed/NCBI
8	Liu W, Zhao X, Zhang YJ, Fang GW and Xue Y: MicroRNA-375 as a potential serum biomarker for the diagnosis, prognosis, and chemosensitivity prediction of osteosarcoma. J Int Med Res. 46:975–983. 2018. View Article : Google Scholar : PubMed/NCBI
9	Xie Y, Sun W, Deng Z, Zhu X, Hu C and Cai L: miR-302b suppresses osteosarcoma cell migration and invasion by targeting Runx2. Sci Rep. 7:133882017. View Article : Google Scholar : PubMed/NCBI
10	Ji Q, Xu X, Li L, Goodman SB, Bi W, Xu M, Xu Y, Fan Z, Maloney WJ, Ye Q, et al: miR-216a inhibits osteosarcoma cell proliferation, invasion and metastasis by targeting CDK14. Cell Death Dis. 8:e31032017. View Article : Google Scholar : PubMed/NCBI
11	Sun Z, Liu Q, Hong H, Zhang H and Zhang T: miR-19 promotes osteosarcoma progression by targeting SOCS6. Biochem Biophys Res Commun. 495:1363–1369. 2018. View Article : Google Scholar : PubMed/NCBI
12	Wu Q, Zhou W, Feng Q, Liu X, Xiong Y and Li H: MicroRNA-92b promotes cell proliferation and invasion in osteosarcoma by directly targeting Dickkopf-related protein 3. Exp Ther Med. 15:173–181. 2018.PubMed/NCBI
13	Zhou C, Jiang CQ, Zong Z, Lin JC and Lao LF: miR-146a promotes growth of osteosarcoma cells by targeting ZNRF3/GSK-3β/β-catenin signaling pathway. Oncotarget. 8:74276–74286. 2017.PubMed/NCBI
14	Zhao Y, Li C, Wang M, Su L, Qu Y, Li J, Yu B, Yan M, Yu Y, Liu B, et al: Decrease of miR-202-3p expression, a novel tumor suppressor, in gastric cancer. PLoS One. 8:e697562013. View Article : Google Scholar : PubMed/NCBI
15	Wang Q, Huang Z, Guo W, Ni S, Xiao X, Wang L, Huang D, Tan C, Xu Q, Zha R, et al: microRNA-202-3p inhibits cell proliferation by targeting ADP-ribosylation factor-like 5A in human colorectal carcinoma. Clin Cancer Res. 20:1146–1157. 2014. View Article : Google Scholar : PubMed/NCBI
16	Deng X, Hou C, Liang Z, Wang H, Zhu L and Xu H: miR-202 suppresses cell proliferation by targeting FOXR2 in endometrial adenocarcinoma. Dis Markers. 2017:28274352017. View Article : Google Scholar : PubMed/NCBI
17	Xu X, Li S, Lin Y, Chen H, Hu Z, Mao Y, Xu X, Wu J, Zhu Y, Zheng X, et al: MicroRNA-124-3p inhibits cell migration and invasion in bladder cancer cells by targeting ROCK1. J Transl Med. 11:2762013. View Article : Google Scholar : PubMed/NCBI
18	Cai SD, Chen JS, Xi ZW, Zhang LJ, Niu ML and Gao ZY: MicroRNA 144 inhibits migration and proliferation in rectal cancer by downregulating ROCK 1. Mol Med Rep. 12:7396–7402. 2015. View Article : Google Scholar : PubMed/NCBI
19	Zheng B, Liang L, Wang C, Huang S, Cao X, Zha R, Liu L, Jia D, Tian Q, Wu J, et al: MicroRNA-148a suppresses tumor cell invasion and metastasis by downregulating ROCK1 in gastric cancer. Clin Cancer Res. 17:7574–7583. 2011. View Article : Google Scholar : PubMed/NCBI
20	An L, Liu Y, Wu A and Guan Y: microRNA-124 inhibits migration and invasion by down-regulating ROCK1 in glioma. PLoS One. 8:e694782013. View Article : Google Scholar : PubMed/NCBI
21	Li J, Song Y, Wang Y, Luo J and Yu W: MicroRNA-148a suppresses epithelial-to-mesenchymal transition by targeting ROCK1 in non-small cell lung cancer cells. Mol Cell Biochem. 380:277–282. 2013. View Article : Google Scholar : PubMed/NCBI
22	Zheng M, Sun X, Li Y and Zuo W: MicroRNA-145 inhibits growth and migration of breast cancer cells through targeting oncoprotein ROCK1. Tumour Biol. 37:8189–8196. 2016. View Article : Google Scholar : PubMed/NCBI
23	Liu X, Choy E, Hornicek FJ, Yang S, Yang C, Harmon D, Mankin H and Duan Z: ROCK1 as a potential therapeutic target in osteosarcoma. J Orthop Res. 29:1259–1266. 2011. View Article : Google Scholar : PubMed/NCBI
24	Cong C, Wang W, Tian J, Gao T, Zheng W and Zhou C: Identification of serum miR-124 as a biomarker for diagnosis and prognosis in osteosarcoma. Cancer Biomark. 21:449–454. 2018. View Article : Google Scholar : PubMed/NCBI
25	Meng X, Chen X, Lu P, Ma W, Yue D, Song L and Fan Q: MicroRNA-202 inhibits tumor progression by targeting LAMA1 in esophageal squamous cell carcinoma. Biochem Biophys Res Commun. 473:821–827. 2016. View Article : Google Scholar : PubMed/NCBI
26	Zhang Y, Zheng D, Xiong Y, Xue C, Chen G, Yan B and Ye Q: miR-202 suppresses cell proliferation in human hepatocellular carcinoma by downregulating LRP6 post-transcriptionally. FEBS Lett. 588:1913–1920. 2014. View Article : Google Scholar : PubMed/NCBI
27	Zhao Z, Lv B, Zhang L, Zhao N and Lv Y: miR-202 functions as a tumor suppressor in non-small cell lung cancer by targeting STAT3. Mol Med Rep. 16:2281–2289. 2017. View Article : Google Scholar : PubMed/NCBI
28	Sun Z, Zhang T, Hong H, Liu Q and Zhang H: miR-202 suppresses proliferation and induces apoptosis of osteosarcoma cells by downregulating Gli2. Mol Cell Biochem. 397:277–283. 2014. View Article : Google Scholar : PubMed/NCBI
29	Zhou F, Li Y, Hao Z, Liu X, Chen L, Cao Y, Liang Z, Yuan F, Liu J, Wang J, et al: MicroRNA-300 inhibited glioblastoma progression through ROCK1. Oncotarget. 7:36529–36538. 2016.PubMed/NCBI
30	Maskey N, Li D, Xu H, Song H, Wu C, Hua K, Song J and Fang L: MicroRNA-340 inhibits invasion and metastasis by downregulating ROCK1 in breast cancer cells. Oncol Lett. 14:2261–2267. 2017. View Article : Google Scholar : PubMed/NCBI
31	Xue H, Guo X, Han X, Yan S, Zhang J, Xu S, Li T, Guo X, Zhang P, Gao X, et al: MicroRNA-584-3p, a novel tumor suppressor and prognostic marker, reduces the migration and invasion of human glioma cells by targeting hypoxia-induced ROCK1. Oncotarget. 7:4785–4805. 2016. View Article : Google Scholar : PubMed/NCBI
32	Majid S, Dar AA, Saini S, Shahryari V, Arora S, Zaman MS, Chang I, Yamamura S, Chiyomaru T, Fukuhara S, et al: MicroRNA-1280 inhibits invasion and metastasis by targeting ROCK1 in bladder cancer. PLoS One. 7:e467432012. View Article : Google Scholar : PubMed/NCBI
33	Lei P, Xie J, Wang L, Yang X, Dai Z and Hu Y: microRNA-145 inhibits osteosarcoma cell proliferation and invasion by targeting ROCK1. Mol Med Rep. 10:155–160. 2014. View Article : Google Scholar : PubMed/NCBI
34	Zhang S, Zhao Y and Wang L: MicroRNA-198 inhibited tumorous behaviors of human osteosarcoma through directly targeting ROCK1. Biochem Biophys Res Commun. 472:557–565. 2016. View Article : Google Scholar : PubMed/NCBI
35	Wang Y, Wang N, Zeng X, Sun J, Wang G, Xu H and Zhao W: MicroRNA-335 and its target Rock1 synergistically influence tumor progression and prognosis in osteosarcoma. Oncol Lett. 13:3057–3065. 2017. View Article : Google Scholar : PubMed/NCBI