Downregulation of microRNA-519 enhances development of lung cancer by mediating the E2F2/PI3K/AKT axis

microRNA-519 下调通过介导 E2F2/PI3K/AKT 轴促进肺癌的发展

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作者:Hua Zhang, Aisikeer Tulahong, Wenran Wang, Yiliyaer Nuerrula, Yuefen Zhang, Ge Wu, Shaya Mahati, Hui Zhu

Abstract

MicroRNA-519 (miR-519) acts as an inhibitor in different kinds of tumors. The current study was set to probe the function of miR-519 in lung cancer and to explore the potential molecular mechanism. The expression difference of miRNAs between lung cancer and paracancerous tissues was analyzed by microarray. miR-519 expression was significantly diminished in lung cancer tissues and cells. After that, EdU staining, CCK-8 assay, Transwell assay, Hoechst 33258 staining and PI/Annexin-V staining revealed that overexpression of miR-519 in lung cancer cells inhibited their viability and promoted apoptosis. TragetScan and miRSearch were employed to predict the target mRNAs of miR-519, which were verified by a luciferase activity assay. miR-519 bound to the 3'untranslated region of E2F transcription factor 2 (E2F2) mRNA. Finally, the extent of PI3K/AKT signaling pathway phosphorylation was examined, which illustrated that upregulation of miR-519 repressed the phosphorylation of the PI3K/AKT pathway in SPC-A-1 and 95C cells. miR-519 reduces PI3K/AKT pathway activities by suppressing the transcription activity of E2F2, thereby potentially inhibiting the occurrence of lung cancer.

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