LncRNA TUG1 promotes the development of osteosarcoma through RUNX2

Sheng,Kunkun; Li,Yan

doi:10.3892/etm.2019.7880

LncRNA TUG1 promotes the development of osteosarcoma through RUNX2

Authors:
- Kunkun Sheng
- Yan Li
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Affiliations: Department of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China
Published online on: August 13, 2019 https://doi.org/10.3892/etm.2019.7880
Pages: 3002-3008
Copyright: © Sheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The lncRNA taurine‑upregulated gene 1 (TUG1) is known to serve a role as an oncogene in the development of a number of human malignancies. However, the functionality of TUG1 in osteosarcoma remains poorly characterized. Therefore, the aim of the present study was to explore the role of TUG1 in osteosarcoma. TUG1 expression in tumor tissues, adjacent healthy tissues and plasma from 40 osteosarcoma patients and 40 healthy controls was detected using reverse transcription‑quantitative PCR. Receiver operating characteristic curves were used to analyze the diagnostic value of TUG1 for osteosarcoma while the prognostic value of TUG1 for osteosarcoma was analyzed using the Kaplan‑Meier method. TUG1 expression vectors and siRNAs were transfected into MG‑63 and U2OS osteosarcoma cell lines, and the effects on osteosarcoma cell viability, migration and invasion were tested using Cell Counting kit‑8 and Transwell assays. The effects of TUG1 overexpression on runt‑related transcription factor 2 (RUNX2) expression were also detected using western blotting. TUG1 expression was found to be significantly higher in osteosarcoma tissues compared with adjacent healthy tissues, and in the plasma of osteosarcoma patients compared with healthy controls. TUG1 expression also exhibited significant diagnostic and prognostic value for osteosarcoma. TUG1 overexpression and knockdown respectively increased and reducedosteosarcoma cell viability, migration and invasion. In addition, TUG1 overexpression upregulated RUNX2 expression. These results suggest that lncRNA TUG1 may promote the development of osteosarcoma by modulating RUNX2 and TUG1 expression, which can serve as prognostic and diagnostic markers for this malignancy.

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1	Durfee RA, Mohammed M and Luu HH: Review of osteosarcoma and current management. Rheumatol Ther. 3:221–243. 2016. View Article : Google Scholar : PubMed/NCBI
2	Lindsey BA, Markel JE and Kleinerman ES: Osteosarcoma overview. Rheumatol Ther. 4:25–43. 2017. View Article : Google Scholar : PubMed/NCBI
3	Lin YH, Jewell BE, Gingold J, Lu L, Zhao R, Wang LL and Lee DF: Osteosarcoma: Molecular pathogenesis and iPSC modeling. Trends Mol Med. 23:737–755. 2017. View Article : Google Scholar : PubMed/NCBI
4	Isakoff MS, Bielack SS, Meltzer P and Gorlick R: Osteosarcoma: Current treatment and a collaborative pathway to success. J Clin Oncol. 33:3029–3035. 2015. View Article : Google Scholar : PubMed/NCBI
5	Esteller M: Non-coding RNAs in human disease. Nat Rev Genet. 12:861–874. 2011. View Article : Google Scholar : PubMed/NCBI
6	Perkel JM: Visiting ‘noncodarnia’. Biotechniques. 54:301, 303–304. 2013. View Article : Google Scholar
7	Li J, Zhang M, An G and Ma Q: LncRNA TUG1 acts as a tumor suppressor in human glioma by promoting cell apoptosis. Exp Biol Med (Maywood). 241:644–649. 2016. View Article : Google Scholar : PubMed/NCBI
8	Xu Y, Wang J, Qiu M and Xu L, Li M, Jiang F, Yin R and Xu L: Upregulation of the long noncoding RNA TUG1 promotes proliferation and migration of esophageal squamous cell carcinoma. Tumor Biol. 36:1643–1651. 2015. View Article : Google Scholar
9	Ma B, Li M, Zhang L, Huang M, Lei JB, Fu GH, Liu CX, Lai QW, Chen QQ and Wang YL: Upregulation of long non-coding RNA TUG1 correlates with poor prognosis and disease status in osteosarcoma. Tumor Biol. 37:4445–4455. 2016. View Article : Google Scholar
10	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
11	Thai P, Statt S, Chen CH, Liang E, Campbell C and Wu R: Characterization of a novel long noncoding RNA, SCAL1, induced by cigarette smoke and elevated in lung cancer cell lines. Am J Respir Cell Mol Biol. 49:204–211. 2013. View Article : Google Scholar : PubMed/NCBI
12	Wang L, Zhao Z, Feng W, Ye Z, Dai W, Zhang C, Peng J and Wu K: Long non-coding RNA TUG1 promotes colorectal cancer metastasis via EMT pathway. Oncotarget. 7:51713–51719. 2016.PubMed/NCBI
13	Kansara M and Thomas DM: Molecular pathogenesis of osteosarcoma. DNA Cell Biol. 26:1–18. 2007. View Article : Google Scholar : PubMed/NCBI
14	Chen X and Yan GY: Novel human lncRNA-disease association inference based on lncRNA expression profiles. Bioinformatics. 29:2617–2624. 2013. View Article : Google Scholar : PubMed/NCBI
15	Yun-Bo F, Xiao-Po L, Xiao-Li L, Guo-Long C, Pei Z and Fa-Ming T: LncRNA TUG1 is upregulated and promotes cell proliferation in osteosarcoma. Open Med (Wars). 11:163–167. 2016.PubMed/NCBI
16	Zhang Q, Geng PL, Yin P, Wang XL, Jia JP and Yao J: Down-regulation of long non-coding RNA TUG1 inhibits osteosarcoma cell proliferation and promotes apoptosis. Asian Pac J Cancer Prev. 14:2311–2315. 2013. View Article : Google Scholar : PubMed/NCBI
17	Hori SS, Lutz AM, Paulmurugan R and Gambhir SS: Correlation of plasma biomarker levels with early-stage tumor viability in an orthotopic ovarian cancer mouse model. Cancer Res. 74 (19 Suppl):Abstract nr 873. 2014.PubMed/NCBI
18	Wang Z, Tan M, Chen G, Li Z and Lu X: LncRNA SOX2-OT is a novel prognostic biomarker for osteosarcoma patients and regulates osteosarcoma cells proliferation and motility through modulating SOX2. IUBMB Life. 69:867–876. 2017. View Article : Google Scholar : PubMed/NCBI
19	Zhang M, Lu W, Huang Y, Shi J, Wu X, Zhang X, Jiang R, Cai Z and Wu S: Downregulation of the long noncoding RNA TUG1 inhibits the proliferation, migration, invasion and promotes apoptosis of renal cell carcinoma. J Mol Histol. 47:421–428. 2016. View Article : Google Scholar : PubMed/NCBI
20	Zhang Q, Geng PL, Yin P, Wang XL, Jia JP and Yao J: Down-regulation of long non-coding RNA TUG1 inhibits osteosarcoma cell proliferation and promotes apoptosis. Asian Pac J Cancer Prev. 14:2311–2315. 2013. View Article : Google Scholar : PubMed/NCBI
21	Rokavec M, Öner MG, Li H, Jackstadt R, Jiang L, Lodygin D, Kaller M, Horst D, Ziegler PK, Schwitalla S, et al: IL-6R/STAT3/miR-34a feedback loop promotes EMT-mediated colorectal cancer invasion and metastasis. J Clin Invest. 124:1853–1867. 2014. View Article : Google Scholar : PubMed/NCBI
22	Martin JW, Zielenska M, Stein GS, van Wijnen AJ and Squire JA: The role of RUNX2 in osteosarcoma oncogenesis. Sarcoma. 2011:2827452011. View Article : Google Scholar : PubMed/NCBI