Impedes Metastatic Behaviors in Hepatocellular Carcinoma via Targeting , , and .

Primary liver cancer accounts for the third most deadly type of malignant tumor globally, and approximately 80% of the cases are hepatocellular carcinoma (HCC), which highly relies on the activity of hypoxia responsive pathways to bolster its metastatic behaviors. MicroRNA-29a () has been shown to exert a hepatoprotective effect on hepatocellular damage and liver fibrosis induced by cholestasis and diet stress, while its clinical and biological role on the activity hypoxia responsive genes including , , and remains unclear. TCGA datasets were retrieved to confirm the differential expression and prognostic significance of all genes in the HCC and normal tissue. The Gene Expression Omnibus (GEO) dataset was used to corroborate the differential expression and diagnostic value of . The bioinformatic identification were conducted to examine the interaction of with , , and . The suppressive activity of on , , and was verified by qPCR, immunoblotting, and luciferase. The effect of overexpression of MIR29A-3p mimics in vitro on apoptosis markers (caspase-9, -3, and poly (ADP-ribose) polymerase (PARP)); cell viability and wound healing performance were examined using immunoblot and a WST-1 assay and a wound healing assay, respectively. The HCC tissue presented low expression of , yet high expression of , , and as compared to normal control. Serum of HCC patients showed decreased levels as compared to that of normal control, with an area under curve (AUC) of 0.751 of a receiver operating characteristic (ROC) curve. Low expression of and high expression of , , and indicated poor overall survival (OS). -3p was shown to target the 3'UTR of , , and . Overexpression of -3p mimic in HepG2 cells led to downregulated gene and protein expression levels of , , and , wherein luciferase reporter assay confirmed that -3p exerts the inhibitory activity via directly binding to the 3'UTR of and . Furthermore, overexpression of -3p mimic induced the activity of caspase-9 and -3 and PARP, while it inhibited the cell viability and wound healing performance. Collectively, this study provides novel insight into a clinical-applicable panel consisting of , , , and and demonstrates an anti-HCC effect of via comprehensively suppressing the expression of , , and , paving the way to a prospective theragnostic approach for HCC.