miR-4484 suppresses hepatocellular carcinoma progression via targeting KIF2C.

Abstract

Aberrantly expressed microRNA-4484 (miR-4484) has recently garnered attention for its involvement in human diseases, but its specific role in hepatocellular carcinoma (HCC) remains largely unexplored. This study investigates the function of miR-4484 in HCC progression and its regulatory interaction with KIF2C. Analysis of the data from the TCGA-LIHC database revealed that miR-4484 expression is significantly downregulated in HCC tissues, with lower levels correlating with worse prognosis. In vitro experiments confirmed that miR-4484 expression is lower in HCC cell lines compared to a normal liver cell line. Functional assays demonstrated that miR-4484 overexpression via a miR-4484 mimic suppressed cell proliferation and induced G1 phase arrest, whereas miR-4484 inhibition promoted proliferation and facilitated cell cycle progression from G1 to S and G2 phases. Additionally, KIF2C expression was significantly upregulated in HCC tissues and cell lines, exhibiting an inverse correlation with miR-4484 levels. Dual-Luciferase Reporter Assays confirmed that miR-4484 directly binds to KIF2C, thereby regulating its expression and influencing cell proliferation and cell cycle progression. In vivo, subcutaneous intratumoral injection of the miR-4484 mimic in nude mice significantly inhibited HCC tumour growth. These findings highlight miR-4484 as a potential tumour suppressor in HCC through its direct targeting of KIF2C, underscoring its promise as a therapeutic target for HCC treatment.