This study investigates the role of microRNA (miRNA) in regulating Mcl-1 protein expression and apoptosis. Mcl-1 is an anti-apoptotic protein that is overexpressed in malignant cells, contributing to resistance to apoptosis. The authors found that mir-29b, a miRNA, negatively regulates Mcl-1 expression by binding to a specific region in the 3' untranslated region (UTR) of the Mcl-1 mRNA. In cholangiocytes, mir-29b was highly expressed, but its expression was downregulated in malignant cholangiocarcinoma cells, leading to increased Mcl-1 protein levels. Transfection of mir-29b into KMCH cells reduced Mcl-1 protein levels and sensitized the cells to TRAIL-induced apoptosis. Conversely, inhibition of mir-29b in non-malignant H69 cells increased Mcl-1 levels and reduced TRAIL-mediated apoptosis. These findings suggest that mir-29b acts as a regulator of Mcl-1 expression and apoptosis, providing a potential target for cancer therapy.This study investigates the role of microRNA (miRNA) in regulating Mcl-1 protein expression and apoptosis. Mcl-1 is an anti-apoptotic protein that is overexpressed in malignant cells, contributing to resistance to apoptosis. The authors found that mir-29b, a miRNA, negatively regulates Mcl-1 expression by binding to a specific region in the 3' untranslated region (UTR) of the Mcl-1 mRNA. In cholangiocytes, mir-29b was highly expressed, but its expression was downregulated in malignant cholangiocarcinoma cells, leading to increased Mcl-1 protein levels. Transfection of mir-29b into KMCH cells reduced Mcl-1 protein levels and sensitized the cells to TRAIL-induced apoptosis. Conversely, inhibition of mir-29b in non-malignant H69 cells increased Mcl-1 levels and reduced TRAIL-mediated apoptosis. These findings suggest that mir-29b acts as a regulator of Mcl-1 expression and apoptosis, providing a potential target for cancer therapy.