Overexpression of miR-148a inhibits viability and invasion of ovarian cancer OVCAR3 cells by targeting FOXO3

miR-148a 过表达通过靶向 FOXO3 抑制卵巢癌 OVCAR3 细胞活力和侵袭

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作者:Dandan Zhu, Donglan Yuan, Runfa Guo, Lixin Zhang, Ting Guo, Yinling Zhao, Jia Wang, Xinping Chen, Hua Qian, Hongshan Ge

Abstract

Decreased expression of microRNA (miR)-148a is associated with poor prognosis in ovarian cancer. The aim of the present study was to investigate the impact of miR-148a on tumor cell viability and invasion via targeting forkhead box protein O3 (FOXO3). Expression of miR-148a was detected in paired tumor and adjacent normal tissues. OVCAR3 cells were transfected with miR-148a mimic and inhibitor. Cell viability, apoptosis and invasion were determined. A luciferase reporter assay was used to study the association between miR-148a and FOXO3. In addition, the influence of miR-148a on tumor cell growth was investigated by performing xenograft assays in nude mice. RT-qPCR showed that miR-148a was downregulated in ovarian cancer tissues. Overexpression of miR-148a in OVCAR3 cells inhibited cell viability, suppressed invasion and promoted cellular apoptosis. The dual-luciferase assay indicated that miR-148a directly regulated the expression of FOXO3, a transcription factor of caspase-3. Western blotting confirmed that the expression of caspase-3 was regulated by the modulation of miR-148a expression. In vivo assays revealed that miR-148a overexpression inhibited the growth of OVCAR3 ×enograft tumors in nude mice. miR-148a is a tumor suppressor in ovarian cancer OVCAR3 cells and in nude mice. The suppressive effect is due to inhibiting cell viability and invasion as well as promoting apoptosis. These results may provide theoretical basis for targeting miR-148a in the treatment of ovarian cancer.

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