首页|RP11-495P10.1 promotes HCC cell proliferation by regulating reprogramming of glucose metabolism and acetylation of the NR4A3 promoter via the PDK1/PDH axis

RP11-495P10.1 promotes HCC cell proliferation by regulating reprogramming of glucose metabolism and acetylation of the NR4A3 promoter via the PDK1/PDH axis

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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.

HCCRP11-495P10.1PDK1glycometabolismNR4A3

Chi Liu、Jie Shi、Zhengyuan Jiang、Shan Jiang、Yuan Wu、Dongqian Peng、Jiebing Tang、Linchi Guo

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Department of Biochemistry & Molecular Biology,Harbin Medical University,Harbin 150000,China

Department of Anatomy and Histology,School of Preclinical Medicine,Chengdu University,Chengdu 610000,China

General Medicine,People's Hospital of Ningxia Hui Autonomous Region,Yinchuan 750000,China

Department of Gastrointestinal Medical Oncology,Harbin Medical University Cancer Hospital,Harbin 150086,China

Department of Endocrinology and Geriatrics,Affiliated Renhe Hospital of Sanxia University,Yichang 443000,China

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Science and Technology Department of NingxiaHaiyan Fund of Harbin Medical University Cancer Hospital

2021AAC03303JJMS2021-13

2024

10.3724/abbs.2023242

生物化学与生物物理学报(英文版)
中国科学院上海生物化学研究所

生物化学与生物物理学报(英文版)

CSTPCD
影响因子：0.772
ISSN：1672-9145
年,卷(期)：2024.56(1)
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