Abstract
The incidence and related death of hepatocellular carcinoma(HCC)have increased over the past decades.However,the molecular mechanisms underlying HCC pathogenesis are not fully understood.Long noncoding RNA(IncRNA)RP11-495P10.1 has been proven to be closely associated with the progression of prostate cancer,but its role and specific mechanism in HCC are still unknown.Here,we identify that RP11-495P10.1 is highly expressed in HCC tissues and cells and contributes to the proliferation of HCC cells.Moreover,this study demonstrates that RP11-495P10.1 affects the proliferation of HCC by negatively regulating the expression of nuclear receptor subfamily 4 group a member 3(NR4A3).Glycometabolism reprogramming is one of the main characteristics of tumor cells.In this study,we discover that RP11-495P10.1 regulates glycometabolism reprogramming by changing the expression of pyruvate dehydrogenase kinase 1(PDK1)and pyruvate dehydrogenase(PDH),thus contributing to the pro-liferation of HCC cells.Furthermore,knockdown of RP11-495P10.1 increases enrichment of H3K27Ac in the pro-moter of NR4A3 by promoting the activity of PDH and the production of acetyl-CoA,which leads to the increased transcription of NR4A3.Altogether,RP11-495P10.1 promotes HCC cell proliferation by regulating the reprogram-ming of glucose metabolism and acetylation of the NR4A3 promoter via the PDK1/PDH axis,which provides an IncRNA-oriented therapeutic strategy for the diagnosis and treatment of HCC.
基金项目
Science and Technology Department of Ningxia(2021AAC03303)
Haiyan Fund of Harbin Medical University Cancer Hospital(JJMS2021-13)
国家科技期刊平台
NSTL
万方数据