WITHDRAWN: Mig-6 Promotes the Apoptosis and Inhibits of the Flux of Autophagy in HCC Cell Lines Through Modulating Mig-6/miR-193a-3p/TGF-β2 Axis

Abstract

<jats:title>Abstract</jats:title> <jats:p><jats:bold>Background:</jats:bold>Mitogen-inducible gene 6 (<jats:italic>Mig-6</jats:italic>) is a tumor suppressor gene that plays an important role in many types of cancers by interacting with EGFR. Thus far, little is known about the molecular mechanism of <jats:italic>Mig-6</jats:italic> in hepatocellular carcinoma (HCC). Also, the relationship between <jats:italic>Mig-6</jats:italic> and miRNAs needs to be elucidated. Therefore, this study first aimed to find whether <jats:italic>Mig-6</jats:italic> could promote apoptosis and inhibition of the flux of autophagy by its downstream miRNA in HCC cell lines. <jats:bold>Methods:</jats:bold> Two cell lines, HepG2and HLE, were used in this study. <jats:italic>Mig-6 </jats:italic>overexpression and knockdown models , miR-193a mimics and inhibitors models,were established. MiRNA microarray profiling were used to verified <jats:italic>Mig-6</jats:italic> regulated- miRNA. Real-time PCR, Western blot analysis were carried out to detect RNA and protein expression.Evaluation of fluorescent LC3 puncta and cell fow cytometer assay were used to test the autophagy and apoptosis respectively. <jats:bold>Results:</jats:bold> <jats:italic>Mig-6</jats:italic> induced the apoptosis and reduced the autophagy of HCC cell lines. MiR-193a-3p is a <jats:italic>Mig-6</jats:italic>-regulated miRNA in <jats:italic>Mig-6 </jats:italic>overexpression model, and miR-193a-3p affected the apoptosis and autophagy of HCC cells by regulating the expression of TGF-β2. Additionally, the relationship between <jats:italic>Mig-6</jats:italic> and transforming growth factor TGF-β2 was explored in depth for the first time.<jats:bold>Conclusion:</jats:bold>These findings revealed an important regulatory axis <jats:italic>Mig-6</jats:italic>/miR-193a-3p/TGF-β2 in the apoptosis and autophagy of HCC cells, providing a novel insight into the therapeutic target in HCC.</jats:p>