Silencing of miR-19a-3p enhances osteosarcoma cells chemosensitivity by elevating the expression of tumor suppressor PTEN

沉默 miR-19a-3p 通过提高肿瘤抑制因子 PTEN 的表达增强骨肉瘤细胞化学敏感性

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作者:Bo Zhang, Yuan Liu, Jiangnan Zhang

Abstract

MicroRNAs (miRNAs/miRs) are small non-coding RNAs, which serve important roles in tumor progression. The present study analyzed the role of miR-19a-3p in the chemosensitivity of osteosarcoma (OS) cells. Overexpression of miR-19a-3p was observed in OS cells and a cisplatin-resistant MG63 cell line was subsequently constructed. It was observed that miR-19a-3p inhibitor transfection suppressed cell proliferation and decreased the expression of Ki67 and PCNA compared with the cisplatin treatment group. miR-19a-3p inhibitor transfection also promoted apoptotic rate, increased the expression of Bcl-2 associated X, apoptosis regulator (Bax) and markedly decreased the expression of Bcl-2 compared with the cisplatin treatment group. These results elucidated that silencing of miR-19a-3p enhanced chemosensitivity of OS cells to Cisplatin, through suppressing cell proliferation and promoting cell apoptosis during treatment with Cisplatin. Bioinformatics study and luciferase reporter assays indicated that PTEN was a target of miR-19a-3p, and western blotting demonstrated that PTEN expression was negatively regulated by miR-19a-3p in OS cells. In addition, overexpression of PTEN decreased cell proliferation, but increased apoptotic rate compared with the cisplatin treatment group. It was observed that inhibition of PTEN by BpV(HOpic) upregulated cell proliferation and downregulated apoptotic rate compared with the Cisplatin-treated miR-19a-3p inhibitor group, indicating that inhibition of PTEN expression counteracted the effect of the miR-19a-3p inhibitor on the regulation of chemosensitivity in OS cells. Taken together, overexpression of miR-19a-3p was observed in OS cell lines and that downregulation of miR-19a-3p enhanced the chemosensitivity of OS cells to Cisplatin, by elevating the expression of the tumor suppressor, PTEN.

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