MiR‑4730 suppresses the progression of liver cancer by targeting the high mobility group A1 pathway.

Abstract

As liver cancer (LC) is the sixth most commonly diagnosed malignancy, it is necessary to elucidate the molecular mechanisms responsible for LC progression. MicroRNAs (miRNAs/miRs) play crucial roles in tumor progression by regulating target gene expression. The present study assessed miRNA-4730 expression and function in LC. The effects of miR-4730 overexpression were examined in LC cell lines, and the target genes of miR-4730 were evaluated using microarray analysis and TargetScan data. In addition, the association between miR-4730 expression in tissue samples and the prognosis of 70 patients with LC was evaluated. miR-4730 expression was suppressed in LC tissues and cell lines. miR-4730 overexpression suppressed cell proliferation and cell cycle progression and promoted apoptosis. High mobility group A1 (HMGA1) was revealed as the direct target of miR-4730 using luciferase reporter assay, and the inhibition of downstream integrin-linked kinase (ILK) expression and Akt or glycogen synthase kinase 3β (GSK3β) phosphorylation was confirmed. The lower expression of miR-4730 in tissue samples was significantly associated with a worse recurrence-free survival of patients with LC. On the whole, miR-4730 suppressed tumor progression by directly targeting HMGA1 and inhibiting the ILK/Akt/GSK3β pathway. miR-4730 thus has potential for use as a prognostic marker and may prove to be a therapeutic target for miRNA-based therapies.