TY - JOUR T1 - Up-regulation of UVRAG by HDAC1 Inhibition Attenuates 5FU-induced Cell Death in HCT116 Colorectal Cancer Cells JF - Anticancer Research JO - Anticancer Res SP - 271 LP - 277 VL - 38 IS - 1 AU - YOON KYUNG JO AU - NA YEON PARK AU - JI HYUN SHIN AU - DOO SIN JO AU - JI-EUN BAE AU - EUN SUN CHOI AU - SUNGHO MAENG AU - HONG BAE JEON AU - SEON AE ROH AU - JONG WOOK CHANG AU - JIN CHEON KIM AU - DONG-HYUNG CHO Y1 - 2018/01/01 UR - http://ar.iiarjournals.org/content/38/1/271.abstract N2 - The ultraviolent irradiation resistance-associated gene (UVRAG), a component of the Beclin 1/autophagy-related 6 complex, regulates the autophagy initiation step and functions in the DNA-damage response. UVRAG is frequently mutated in various cancer types, and mutations of UVRAG increase sensitivity to chemotherapy by impairing DNA-damage repair. In this study, we addressed the epigenetic regulation of UVRAG in colorectal cancer cells. UVRAG expression was increased in cells treated with histone deacetylase (HDAC) inhibitors, such as valproic acid and suberoylanilide hydroxamic acid. Down-regulation of HDAC1 enhanced UVRAG expression in colorectal cancer cells. In addition, both chemical and genetic inhibition of HDAC1 reduced the activation of caspase-3 and cytotoxicity in 5-fluorouracil (5FU)-treated cancer cells. In contrast, UVRAG overexpression inhibited caspase activation and cell death in 5FU-treated cells. Taken together, our findings suggest that up-regulation of UVRAG by HDAC1 inhibition potentiates DNA-damage–mediated cell death in colorectal cancer cells. ER -