RT Journal Article
SR Electronic
T1 Camptothecin Induces Apoptosis in Cancer Cells via miR-125b Mediated Mitochondrial Pathways
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP mol.111.076794
DO 10.1124/mol.111.076794
A1 Cheng-Wu Zeng
A1 Xing-Ju Zhang
A1 Kang-Yu Lin
A1 Hua Ye
A1 Shu-Ying Feng
A1 Hua Zhang
A1 Yue-Qin Chen
YR 2012
UL http://molpharm.aspetjournals.org/content/early/2012/01/17/mol.111.076794.abstract
AB Camptothecin (CPT) is an effective chemotherapeutic agent for treatment of cancer patients. The mechanisms underlying CPT-mediated responses in cancer cells are not fully understood. MicroRNA (miRNA) play important roles in tumorigenesis and drug sensitivity. However, the interaction between camptothecin and miRNA has not been previously explored. In this study, we verified that miR-125b was down-regulated in CPT-induced apoptosis in cancer cells and that ectopic expression of miR-125b partially restored cell viability and inhibited cell apoptosis that was induced by CPT. In addition, we demonstrated that CPT induced apoptosis in cancer cells by miR-125b mediated mitochondrial pathways via targeting to the 3¡¯UTR regions of Bak1, Mcl1 and p53. A significant increase in Bak1, Mcl1 and p53 protein levels was detected in response to the treatments of CPT. Notably, the expression levels of Bak1, Mcl1 and p53 increased in a time-dependent manner and negatively correlated with miR-125b expression. Interestingly, we revealed that miR-125b directly targeted the 3¡¯UTR regions of multiple genes in a CPT-induced mitochondrial pathway. In addition, most targets of miR-125b were pro-apoptotic genes, whereas some of the targets were anti-apoptotic genes. We hypothesized that miR-125b may mediate the activity of chemotherapeutic agents to induce apoptosis by regulating multiple targets. This is the first report to show that camptothecin induces cancer cell apoptosis via miRNA mediated mitochondrial pathways. The results suggest that suppression of miR-125b may be a novel approach for the treatment of cancer.