MicroRNA-361-5p induces hepatocellular carcinoma cell apoptosis and enhances drug sensitivity by targeting MAP3K9

MicroRNAs (miRs) participate in the development of several cancers. miR-361-5p suppresses the proliferation of hepatocellular carcinoma (HCC) cells. However, its function and potential underlying mechanism of action in the chemoresistance of HCC remains unknown. Therefore, cisplatin (DDP)-resistant HCC cells were used to study the role and potential mechanism of action of miR-361-5p in HCC resistance to chemotherapy. TargetScan software and dual-luciferase reporter assays were used to determine whether MAPK kinase kinase 9 (MAP3K9) is a target gene of miR-361-5p. Subsequently, reverse transcription-quantitative PCR and western blot analyses demonstrated that miR-361-5p mimic decreased MAP3K9 expression levels in Huh7 cells and this change was reversed by transfection with the MAP3K9-plasmid. In addition, compared with THLE-2 cells, miR-361-5p was downregulated, while MAP3K9 was upregulated in Huh7 cells. MAP3K9 also reversed the miR-361-5p-induced HCC cell apoptosis. A DDP-resistant cell line, Huh7/DDP, was established and MTT analysis revealed that the IC(50) value of DDP treatment in Huh7/DDP cells was higher compared with that in Huh7 cells. miR-361-5p expression was lower in Huh7/DDP cells compared with that in Huh7 cells. Similarly, miR-361-5p downregulated the expression levels of MAP3K9 in Huh7/DDP cells. Furthermore, MAP3K9 reversed miR-361-5p-induced sensitivity of Huh7/DDP cells to DDP and miR-361-5p induced Huh7/DDP cell apoptosis. Therefore, the findings of the present study demonstrated that the miR-361-5p/MAP3K9 axis may serve as a new potential biomarker and therapeutic target for DDP-resistant HCC.