MicroRNA 196B regulates FAS-mediated apoptosis in colorectal cancer cells

// Ji-Su Mo 1,* , Khondoker Jahengir Alam 1,* , In-Hong Kang 1 , Won Cheol Park 2 , Geom-Seog Seo 3 , Suck-Chei Choi 3 , Hun-Soo Kim 1 , Hyung-Bae Moon 1 , Ki-Jung Yun 1,3 and Soo-Cheon Chae 1,3 1 Department of Pathology, School of Medicine, Wonkwang University, Iksan, Chonbuk, Republic of Korea 2 Department of Surgery, School of Medicine, Wonkwang University, Iksan, Chonbuk, Republic of Korea 3 Digestive Disease Research Institute, Wonkwang University, Iksan, Chonbuk, Republic of Korea * These authors contributed equally to this work Correspondence: Soo-Cheon Chae, email: // Keywords : Fas, MIR196B, Colorectal cancer, Apoptosis Received : August 11, 2014 Accepted : December 22, 2014 Published : December 26, 2014 Abstract Using miRNA microarray analysis, we identified 31 miRNAs that were significantly up-regulated or down-regulated in colon cancer tissues. We chose MIR196B, which was specifically up-regulated in colon cancer, for further study. We identified 18 putative MIR196B target genes by comparing between the mRNAs down-regulated in MIR196B-overexpressed cells and the assumed MIR196B target genes predicted by public bioinformatics tools. The association between MIR196B and FAS was verified in this study. FAS expression was constitutively elevated in normal human colorectal tissues. However, its expression was often reduced in human colorectal cancer. The decrease in FAS expression could be responsible for the reduction of apoptosis in colorectal cancer cells. In colorectal cancer tissue, we showed that MIR196B up-regulation was mutually followed by down regulation of FAS expression. We also showed that MIR196B directly repressed FAS expression in colorectal cells. Furthermore, anti-MIR196B up-regulated FAS expression and increased apoptosis in colorectal cancer cell lines. Our results suggest that the up-regulation of MIR196B modulates apoptosis in colorectal cancer cells by partially repressing FAS expression and that anti-MIR196B could be a potential candidate as an anti-cancer drug in colorectal cancer therapy.