Eur Rev Med Pharmacol Sci 2019; 23 (16): 6813-6823
DOI: 10.26355/eurrev_201908_18720

LINC01116 promotes proliferation, invasion and migration of osteosarcoma cells by silencing p53 and EZH2

Z.-F. Zhang, H.-H. Xu, W.-H. Hu, T.-Y. Hu, X.-B. Wang

Pain Treatment Center, The Second Hospital of Tianjin Medical University, Tianjin, China. hdwangxb@163.com


OBJECTIVE: The aim of this study was to elucidate the expression pattern and potential function of LINC01116 in regulating the progression of osteosarcoma.

PATIENTS AND METHODS: Expression levels of LINC01116 in osteosarcoma tissues (n=52) and adjacent normal tissues (n=52) were detected by quantitative Real-time polymerase chain reaction (qRT-PCR). Survival analysis and univariate analysis were performed in osteosarcoma patients based on the relative expression levels of LINC01116 and clinical data. Overexpression or silence of LINC01116 in osteosarcoma cells was achieved by transfection of plasmid complementary deoxyribonucleic acid (pcDNA)-LINC01116 or si-LINC01116, respectively. Subsequently, the regulatory effects of LINC01116 on cellular behaviors of osteosarcoma cells were examined by cell counting kit-8 (CCK-8), transwell and flow cytometry. Meanwhile, the potential mechanism of LINC01116 in regulating the progression of osteosarcoma was explored by RNA binding protein immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP) and Western blot. Potential target genes in osteosarcoma were searched, and their functions were clarified through a series of rescue experiments.

RESULTS: LINC01116 expression in osteosarcoma tissues was significantly higher than adjacent normal tissues. The expression of LINC01116 was negatively correlated with overall survival, whereas positively correlated with tumor size and clinical grade of osteosarcoma patients. Transfection of pcDNA-LINC01116 significantly enhanced proliferative, migratory and invasive abilities of U2OS cells, shortened G0/G1 phase period, and inhibited cell apoptosis. However, transfection of si-LINC01116 in MG63 cells obtained the opposite trends in the above-mentioned cellular behaviors. Furthermore, RIP assay confirmed the binding of enhancer of zeste homolog 2 (EZH2) to LINC01116. Knockdown of LINC01116 significantly up-regulated the expressions of phosphatase and tensin homolog deleted on chromosome ten (PTEN) and p53. Moreover, EZH2 knockdown could reverse the inhibitory effect of LINC01116 on carcinogenesis of osteosarcoma.

CONCLUSIONS: LINC01116 is highly expressed in osteosarcoma. Up-regulated LINC01116 can promote cell proliferation, invasion and cell cycle progression, while inhibiting the apoptosis of osteosarcoma cells. Furthermore, LINC01116 is involved in the development of osteosarcoma by binding to EZH2 to regulate expressions of PTEN and p53.

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To cite this article

Z.-F. Zhang, H.-H. Xu, W.-H. Hu, T.-Y. Hu, X.-B. Wang
LINC01116 promotes proliferation, invasion and migration of osteosarcoma cells by silencing p53 and EZH2

Eur Rev Med Pharmacol Sci
Year: 2019
Vol. 23 - N. 16
Pages: 6813-6823
DOI: 10.26355/eurrev_201908_18720