Knockdown of miR-106a suppresses migration and invasion and enhances radiosensitivity of hepatocellular carcinoma cells by upregulating FBXW7

miR-106a 敲低通过上调 FBXW7 抑制肝癌细胞迁移和侵袭并增强其放射敏感性

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作者:Peng Deng, Yuni Wu

Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. microRNAs (miRNAs) have been reported to play essential roles in HCC progression and radiosensitivity. However, the effect of miR-106a on HCC progression and radiosensitivity as well as its mechanism remain largely unknown. The expressions of miR-106a and F-box and WD repeat domain containing 7 (FBXW7) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot, respectively. Cell migration and invasion were analyzed by trans-well assay. The radiosensitivity was investigated by colony formation and western blot. The interaction between miR-106a and FBXW7 was explored by luciferase activity and RNA immunoprecipitation (RIP) analyses. Then miR-106a expression was elevated in HCC tissues and cells and associated with tumor stage as well as overall survival. Knockdown of miR-106a impeded cell migration and invasion but contributed to irradiation-induced inhibition of survival and increase of phosphorylation of histone in Serine 139 (γ-H2AX) protein in HCC cells. Moreover, FBXW7 was indicated as a target of miR-106a and negatively correlated with miR-106a. Besides, interference of FBXW7 reversed the regulatory effect of miR-106a abrogation on migration, invasion and radiosensitivity in HCC cells. The results showed down-regulation of miR-106a suppressed migration and invasion and increased radiosensitivity of HCC cells by targeting FBXW7, providing a novel avenue for HCC treatment.

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