HA117 endows HL60 cells with a stem-like signature by inhibiting the degradation of DNMT1 via its ability to down-regulate expression of the GGL domain of RGS6

摘要: All-trans retinoic acid (ATRA) induces complete remission in almost all patients with acute promyelocytic leukemia (APL) via its ability to induce the vivo differentiation of APL blasts. However, prolonged ATRA treatment can result drug resistance. In previous studies, we generated a multi-drug-resistant HL60/ATRA cell line and found it contain new resistance-related gene segment, HA117. this study, demonstrate that subpopulations HL60 cells putative stem-like signature by up-regulating expression segment Western blot analysis quantitative real-time PCR demonstrated HA117 causes alternative splicing regulator G-protein signaling 6 (RGS6) down-regulation GGL domain RGS6, which plays an important role DNA methyltransferase 1 (DNMT1) degradation. Moreover, DNMT1 was increased multi-drug resistance cells. Knockdown restored blocked expression. resistant displayed cancer steam markers CD133 CD123. The stem marker, Nanog, significantly up-regulated. conclusion, our study shows potentially promotes inhibiting ubiquitination degradation down-regulating RGS6. These results throw light on cellular events associated ATRA-induced phenotype leukemia.