The Role And Mechanism Of MiR-4458 In Human Hepatocellular Carcinoma

Objective: To investigate the role and mechanism of miR-4458 in human hepatocellular carcinoma(HCC).Method:(1)The expression of miR-4458 in 23 pairs of HCC tissues and their matched para-carcinoma tissues were detected by qRT-PCR.The Kaplan-Meier Plotter was utilized to analyze the correlation between miR-4458 expression and overall survival of HCC patients.(2)The expression of miR-4458 was regulated in Hep3 B and Huh7 HCC cell lines.The effect of miR-4458 expression on HCC cell migration and invasion was verified using wound-healing assay and transwell assay.In addition,Western blot was performed to measure the protein levels of the epithelial-mesenchymal transition(EMT)markers E-Cadherin,N-Cadherin,Vimentin,and Snail.(3)The effect of miR-4458 on the target gene and pathway factors was tested by qRT-PCR and western blot.Results:(1)Our results revealed that the expression of miR-4458 was significantly lower in HCC tissues than in their matched para-carcinoma tissues.Low expression of miR-4458 indicated poor overall survival.(2)Forced overexpression of miR-4458 inhibited the migration,invasion,andEMT of HCC cells,while downregulation of miR-4458 promoted the aggressive phenotype.(3)miR-4458 overexpression inhibited the expression of TGFBR1.Furthermore,miR-4458 suppressed the expression of p-Smad2/3,the key factor of TGF-? signaling pathway,by inhibiting TGFBR1.Conclusion: miR-4458 inhibits the migration,invasion,and EMT of HCC cells by suppressing TGF-? signaling pathway via targeting TGFBR1.The study provides novel insights into molecular mechanism of miR-4458,and identifies miR-4458 as a new therapeutic strategy for HCC.