lncRNA SNHG1 negatively regulates miRNA‑101‑3p to enhance the expression of ROCK1 and promote cell proliferation, migration and invasion in osteosarcoma

Deng,Rui; Zhang,Jinyuan; Chen,Jianting

doi:10.3892/ijmm.2018.4039

lncRNA SNHG1 negatively regulates miRNA‑101‑3p to enhance the expression of ROCK1 and promote cell proliferation, migration and invasion in osteosarcoma

Authors:
- Rui Deng
- Jinyuan Zhang
- Jianting Chen
View Affiliations

Affiliations: Department of Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
Published online on: December 20, 2018 https://doi.org/10.3892/ijmm.2018.4039
Pages: 1157-1166
Copyright: © Deng 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

Osteosarcoma (OS) is a rare malignant bone tumor that commonly occurs in children and adolescents and causes pain and swelling of the long bones of the legs and arms. Long non‑coding RNA (lncRNA) and micro (mi)RNA‑101 are important in the initialization and progression of OS. However, the mechanism underlying the role of the lncRNA and miRNA‑101 in OS remains to be fully elucidated. In the present study, through reverse transcription‑quantitative polymerase chain reaction analysis, it was first found that the lncRNA SNHG1 was upregulated and miRNA‑101‑3p was downregulated in OS tissues and cell lines. Second, the knockdown of lncRNA SNHG1 induced cell apoptosis and maintained the cell cycle at the G0/G1 phase, which decreased the overall cell viability. Furthermore, according to a dual‑luciferase assay and western blot analysis, miRNA‑101‑3p was found to be a target of the lncRNA SNHG1 in OS, which further regulated the expression of Rho‑associated coiled‑coil‑containing protein kinase 1 (ROCK1). It was found that the phosphoinositide 3‑kinase/ATK pathway was inactivated and that epithelial‑mesenchymal transition was activated in OS cell lines with overexpression of the lncRNA SNHG1. Taken together, in OS cell lines, the lncRNA SNHG1 acted as an oncogene, and miRNA‑101‑3p was considered a tumor suppressor. The lncRNA SNHG1 promoted OS cell proliferation, migration and invasion by downregulating the expression of miRNA‑101‑3p, which enhanced the expression of ROCK1.

View Figures

View References

1	Lamoureux F, Trichet V, Chipoy C, Blanchard F, Gouin F and Redini F: Recent advances in the management of osteosarcoma and forthcoming therapeutic strategies. Expert Rev Anticancer Ther. 7:169–181. 2007. View Article : Google Scholar : PubMed/NCBI
2	Wang Z, He R, Xia H, Wei YU and Wu S: MicroRNA-101 has a suppressive role in osteosarcoma cells through the targeting of c-FOS. Exp Ther Med. 11:1293–1299. 2016. View Article : Google Scholar : PubMed/NCBI
3	Marina N, Gebhardt M, Teot L and Gorlick R: Biology and therapeutic advances for pediatric osteosarcoma. Oncologist. 9:422–441. 2004. View Article : Google Scholar : PubMed/NCBI
4	Guo J, Reddick WE, Glass JO, Ji Q, Billups CA, Wu J, Hoffer FA, Kaste SC, Jenkins JJ, Ortega Flores XC, et al: Dynamic contrast-enhanced magnetic resonance imaging as a prognostic factor in predicting event-free and overall survival in pediatric patients with osteosarcoma. Cancer. 118:3776–3785. 2012. View Article : Google Scholar
5	El-Naggar AM, Veinotte CJ, Cheng H, Grunewald TG, Negri GL, Somasekharan SP, Corkery DP, Tirode F, Mathers J, Khan D, et al: Translational Activation of HIF1α by YB-1 Promotes Sarcoma Metastasis. Cancer Cell. 27:682–697. 2015. View Article : Google Scholar : PubMed/NCBI
6	Kansara M, Teng MW, Smyth MJ and Thomas DM: Translational biology of osteosarcoma. Nat Rev Cancer. 14:722–735. 2014. View Article : Google Scholar : PubMed/NCBI
7	Macfarlane LA and Murphy PR: MicroRNA: Biogenesis, Function and Role in Cancer. Curr Genomics. 11:537–561. 2010. View Article : Google Scholar
8	Yang J and Zhang W: New molecular insights into osteosarcoma targeted therapy. Curr Opin Oncol. 25:398–406. 2013. View Article : Google Scholar : PubMed/NCBI
9	Wang HJ, Ruan HJ, He XJ, Ma YY, Jiang XT, Xia YJ, Ye ZY and Tao HQ: MicroRNA-101 is down-regulated in gastric cancer and involved in cell migration and invasion. Eur J Cancer. 46:2295–2303. 2010. View Article : Google Scholar : PubMed/NCBI
10	Zhang JG, Guo J-F, Liu D-L, Liu Q and Wang J-J: MicroRNA-101 exerts tumor-suppressive functions in non-small cell lung cancer through directly targeting enhancer of zeste homolog 2. J Thorac Oncol. 6:671–678. 2011. View Article : Google Scholar : PubMed/NCBI
11	Esquela-Kerscher A and Slack FJ: Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar : PubMed/NCBI
12	Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI
13	Wu Q, Jin H, Yang Z, Luo G, Lu Y, Li K, Ren G, Su T, Pan Y, Feng B, et al: MiR-150 promotes gastric cancer proliferation by negatively regulating the pro-apoptotic gene EGR2. Biochem Biophys Res Commun. 392:340–345. 2010. View Article : Google Scholar : PubMed/NCBI
14	Ma Y, Zhang P, Wang F, Zhang H, Yang J, Peng J, Liu W and Qin H: miR-150 as a potential biomarker associated with prognosis and therapeutic outcome in colorectal cancer. Gut. 61:1447–1453. 2012. View Article : Google Scholar
15	Farhana L, Dawson MI, Murshed F, Das JK, Rishi AK and Fontana JA: Upregulation of miR-150* and miR-630 induces apoptosis in pancreatic cancer cells by targeting IGF-1R. PLoS One. 8:e610152013. View Article : Google Scholar
16	Hu H, Zhang Y, Cai XH, Huang JF and Cai L: Changes in microRNA expression in the MG-63 osteosarcoma cell line compared with osteoblasts. Oncol Lett. 4:1037–1042. 2012. View Article : Google Scholar : PubMed/NCBI
17	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
18	Aguda BD, Kim Y, Piper-Hunter MG, Friedman A and Marsh CB: MicroRNA regulation of a cancer network: Consequences of the feedback loops involving miR-17-92, E2F, and Myc. Proc Natl Acad Sci USA. 105:19678–19683. 2008. View Article : Google Scholar : PubMed/NCBI
19	Cui Y, Zhang F, Zhu C, Geng L, Tian T and Liu H: Upregulated lncRNA SNHG1 contributes to progression of non-small cell lung cancer through inhibition of miR-101-3p and activation of Wnt/β-catenin signaling pathway. Oncotarget. 8:17785–17794. 2017.PubMed/NCBI
20	Jin J, Chu Z, Ma P, Meng Y and Yang Y: Long non-coding RNA SPRY4-IT1 promotes proliferation and invasion by acting as a ceRNA of miR-101-3p in colorectal cancer cells. Tumour Biol. 39:10104283177162502017. View Article : Google Scholar : PubMed/NCBI
21	Li CY, Pang YY, Yang H, Li J, Lu HX, Wang HL, Mo WJ, Huang LS, Feng ZB and Chen G: Identification of miR-101-3p targets and functional features based on bioinformatics, meta-analysis and experimental verification in hepatocellular carcinoma. Am J Transl Res. 9:2088–2105. 2017.PubMed/NCBI
22	Jiang R, Zhang C, Liu G, Gu R and Wu H: MicroRNA-101 inhibits proliferation, migration and invasion in osteosarcoma cells by targeting ROCK1. Am J Cancer Res. 7:88–97. 2017.PubMed/NCBI
23	Chang Z, Huo L, Li K, Wu Y and Hu Z: Blocked autophagy by miR-101 enhances osteosarcoma cell chemosensitivity in vitro. ScientificWorldJournal. 2014:7947562014. View Article : Google Scholar : PubMed/NCBI
24	Zhang K, Zhang Y, Ren K, Zhao G, Yan K and Ma B: MicroRNA-101 inhibits the metastasis of osteosarcoma cells by downregulation of EZH2 expression. Oncol Rep. 32:2143–2149. 2014. View Article : Google Scholar : PubMed/NCBI
25	Lin S, Shao NN, Fan L, Ma XC, Pu FF and Shao ZW: Effect of microRNA-101 on proliferation and apoptosis of human osteosarcoma cells by targeting mTOR. J Huazhong Univ Sci Technolog Med Sci. 34:889–895. 2014. View Article : Google Scholar : PubMed/NCBI
26	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
27	Fatica A and Bozzoni I: Long non-coding RNAs: New players in cell differentiation and development. Nat Rev Genet. 15:7–21. 2014. View Article : Google Scholar
28	Ponting CP, Oliver PL and Reik W: Evolution and functions of long noncoding RNAs. Cell. 136:629–641. 2009. View Article : Google Scholar : PubMed/NCBI
29	Fang Y and Fullwood MJ: Roles, Functions, and Mechanisms of Long Non-coding RNAs in Cancer. Genomics Proteomics Bioinformatics. 14:42–54. 2016. View Article : Google Scholar : PubMed/NCBI
30	Mouraviev V, Lee B, Patel V, Albala D, Johansen TE, Partin A, Ross A and Perera RJ: Clinical prospects of long noncoding RNAs as novel biomarkers and therapeutic targets in prostate cancer. Prostate Cancer Prostatic Dis. 19:14–20. 2016. View Article : Google Scholar
31	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
32	Villalonga P, Fernández de Mattos S and Ridley AJ: RhoE inhibits 4E-BP1 phosphorylation and eIF4E function impairing cap-dependent translation. J Biol Chem. 284:35287–35296. 2009. View Article : Google Scholar : PubMed/NCBI
33	Whatcott CJ, Ng S, Barrett MT, Hostetter G, Von Hoff DD and Han H: Inhibition of ROCK1 kinase modulates both tumor cells and stromal fibroblasts in pancreatic cancer. PLoS One. 12:e01838712017. View Article : Google Scholar : PubMed/NCBI
34	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
35	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
36	Wang Y, Liang T, Wang Y, Huang Y and Li Y: Long non-coding RNA AK093407 promotes proliferation and inhibits apoptosis of human osteosarcoma cells via STAT3 activation. Am J Cancer Res. 7:892–902. 2017.PubMed/NCBI
37	Jiang Z, Jiang C and Fang J: Up-regulated lnc-SNHG1 contributes to osteosarcoma progression through sequestration of miR-577 and activation of WNT2B/Wnt/β-catenin pathway. Biochem Biophys Res Commun. 495:238–245. 2018. View Article : Google Scholar
38	Wang J, Cao L, Wu J and Wang Q: Long non-coding RNA SNHG1 regulates NOB1 expression by sponging miR-326 and promotes tumorigenesis in osteosarcoma. Int J Oncol. 52:77–88. 2018.
39	Li HJ, Li X, Pang H, Pan JJ, Xie XJ and Chen W: Long non-coding RNA UCA1 promotes glutamine metabolism by targeting miR-16 in human bladder cancer. Jpn J Clin Oncol. 45:1055–1063. 2015. View Article : Google Scholar : PubMed/NCBI
40	Zeisberg M and Neilson EG: Biomarkers for epithelial-mesenchymal transitions. J Clin Invest. 119:1429–1437. 2009. View Article : Google Scholar : PubMed/NCBI