Targeted regulation of miR-218 on BIRC5 for hepatocellular carcinoma apoptosis and proliferation

Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) inhibits apoptosis via suppressing Caspase activity. Elevated BIRC5 is correlated with occurrence of hepatocellular carcinoma (HCC). Lower miR-218 expression occurs in HCC tissues, indicating it tumor suppressor role in HCC. Bioinformatics analysis showed satisfactory targeting relationship between miR-218 and 3'-UTR of BIRC5 mRNA. This study thus investigated the role of miR-218 in regulating BIRC5 expression and HCC pathogenesis. HCC tumor and adjacent tissues were tested for miR-218 and BIRC5 expression. Cultured MHCC97-H, MHCC97-L and HL-7702 cells were tested for Ki-67 expression and basal apoptosis, in addition to miR-218 and BIRC5 expressions. Dual luciferase reporter gene assay was used to confirm targeted regulation between miR-218 and BIRC5. In vitro cultured MHCC97-H cells were treated with miR-218 mimic and/or si-BIRC5. Cell apoptosis, proliferation and protein expression of BIRC and cleaved Caspase-3 were examined by flow cytometry, MTT and Western blot. Compared to adjacent tissues, HCC tissues had lower miR-218 and higher BIRC5 expression. Cultured HCC cells had higher BIRC5 and Ki-67 levels than normal cells, whilst miR-218 expression and basal apoptosis were decreased. MiR-218 targeted and suppressed BIRC5 expression. Transfection of miR-218 mimic and/or si-BIRC5 also decreased BIRC5 expression in HCC cells, decreased its inhibitory role on Caspase-3 activity, enhanced cell apoptosis and suppressed proliferation. MiR-218 is down-regulated in HCC tissues whilst BIRC5 expression is elevated. MiR-218 can enhance Caspase-3 activity via targeted inhibition on BIRC5 expression, thus potentiating Caspase-3 activity and facilitating HCC apoptosis whilst inhibiting proliferation.