HLA-DQB1-AS1通过结合ZRANB2蛋白促进肝细胞癌细胞增殖并抑制凋亡

Abstract

Major histocompatibility complex, class II, DQ beta 1 antisense RNA 1 (HLA-DQB1-AS1) conferred the susceptibility to hepatocellular carcinoma. Sustaining cell growth and resisting apoptosis are two hallmarks of hepatocellular carcinoma. The present study explored the role of HLA-DQB1-AS1 in the proliferation and apoptosis of hepatocellular carcinoma cells and investigated its downstream pathway. Colony formation assay was performed to assess cell proliferation. Cell apoptosis was assessed with the TdT-mediated dUTP nick end labeling method. HLA-DQB1-AS1 deficiency exerts antiproliferative and proapoptotic effects on hepatocellular carcinoma cells. Moreover, based on bioinformatic analysis combined with the results of RNA immunoprecipitation assay, HLA-DQB1-AS1 was revealed to bind with zinc finger RANBP2-type containing 2 (ZRANB2) protein. ZRANB2 was upregulated in hepatocellular carcinoma at a clinical and cellular level. HLA-DQB1-AS1 caused no significant effects on ZRANB2 mRNA and protein expression. ZRANB2 knockdown suppressed cell proliferation and enhanced cell apoptosis of hepatocellular carcinoma. Moreover, ZRANB2 overexpression rescued the anticancer effect of silenced HLA-DQB1-AS1 in hepatocellular carcinoma cells. In conclusion, HLA-DQB1-AS1 promotes cell proliferation and inhibits apoptosis in hepatocellular carcinoma by the interaction with ZRANB2 protein.