Mcl-1 Is a Novel Target of miR-26b That Is Associated with the Apoptosis Induced by TRAIL in HCC Cells

الملخص EN

Aim.

To investigate the role of miR-26b and Mcl-1 in TRAIL-inducing cell death in hepatocellular carcinoma.

Methods.

The expression of miR-26b and Mcl-1 in HCC was detected by RT-qPCR and western blot.

The regulation of Mcl-1 by miR-26b was determined by luciferase reporter assay.

MTT and flow cytometry were employed to detect the cell viability and apoptosis.

Results.

miR-26b is commonly downregulated in HCC cell lines compared with the LO2 cell line.

In contrast, the Mcl-1 expression is upregulated in HCC cell lines.

Bioinformatic analysis identified a putative target site in the Mcl-1 mRNA for miR-26b and luciferase reporter assay showed that miR-26b directly targeted the 3′-UTR (3′-Untranslated Regions) of Mcl-1 mRNA.

Transfection of miR-26b mimics suppressed Mcl-1 expression in HCC cells and sensitized the cancer cells to TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) cytotoxicity.

In addition, transfection of HCC cells with Mcl-1 expression plasmid abolished the sensitization effect of miR-26b to TRAIL-inducing apoptosis.

Conclusions.

Our study showed that miR-26b was a negative regulator of Mcl-1 gene and sensitized TRAIL-inducing apoptosis in HCC cells, suggesting that the miR-26b-Mcl-1 pathway might be a novel target for the treatment of HCC.