HIF-2 alpha-induced upregulation of CD36 promotes the development of ccRCC

作者全名："Liao, Meng; Li, Yiyu; Xiao, Anhua; Lu, Qianlan; Zeng, Han; Qin, Hong; Zheng, Enze; Luo, Xiaoqing; Chen, Lin; Ruan, Xiong Z.; Yang, Ping; Chen, Yaxi"

作者地址："[Liao, Meng; Li, Yiyu; Xiao, Anhua; Lu, Qianlan; Zeng, Han; Qin, Hong; Zheng, Enze; Luo, Xiaoqing; Chen, Lin; Ruan, Xiong Z.; Yang, Ping; Chen, Yaxi] Chongqing Med Univ, Affiliated Hosp 2, Ctr Lipid Res, Chongqing 400016, Peoples R China; [Liao, Meng; Li, Yiyu; Xiao, Anhua; Lu, Qianlan; Zeng, Han; Qin, Hong; Zheng, Enze; Luo, Xiaoqing; Chen, Lin; Ruan, Xiong Z.; Yang, Ping; Chen, Yaxi] Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Dept Infect Dis,Key Lab Mol Biol Infect Dis,Minist, Chongqing 400016, Peoples R China; [Ruan, Xiong Z.] UCL, Med Sch, Ctr Nephrol, John Moorhead Res Lab, Royal Free Campus, London NW3 2PF, England"

通信作者："Yang, P; Chen, YX (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Ctr Lipid Res, Chongqing 400016, Peoples R China.; Yang, P; Chen, YX (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Dept Infect Dis,Key Lab Mol Biol Infect Dis,Minist, Chongqing 400016, Peoples R China."

来源：EXPERIMENTAL CELL RESEARCH

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000880834100004

JCR分区：Q2

影响因子：3.7

年份：2022

卷号：421

期号：2

开始页：　

结束页：　

文献类型：Article

关键词：CD36; Hypoxia; HIF-2?; Lipid; ccRCC

摘要："Clear cell renal cell carcinoma (ccRCC) is characterized by the abundance of lipid droplets and the activation of the hypoxia-inducible factor (HIF) signaling pathway. However, the lipid reprogramming induced by HIF signaling in ccRCC is not fully understood. In this study, we found that the fatty acid receptor CD36 was highly expressed in human ccRCC tissues and ccRCC cell lines. CD36 overexpression increased fatty acid uptake and lipid droplet formation, and enhanced the proliferation and migration of ccRCC cells in a DGAT1-dependent manner. In contrast, the disruption of endogenous CD36 showed the opposite effects. The upregulated expres-sion of CD36 in ccRCC was associated with hypoxia and HIF-2 alpha activation. Furthermore, we identified CD36 as a new target of the transcription factor HIF-2 alpha. The knockdown of CD36 in ccRCC cells reduced lipid accumulation and also blocked the tumor-promoting effects induced by HIF-2 alpha under hypoxia. Our findings suggest that hypoxia-dependent HIF-2 alpha promotes the remodeling of lipid metabolism and the malignant phenotype of ccRCC via CD36, providing a certain theoretical basis for clarifying the mechanism of ccRCC."

基金机构：National Natural Science Foundation of China; National Key R&D Program of China; Chongqing Research Program of Basic Research and Frontier Technology; Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University; 111 Project; [81873569]; [32030054]; [2018YFC1312700]; [cstc2020jcyj-zdxmX0007]; [cstc2020jcyj-msxmX0205]; [[2021] 24]; [D20028]

基金资助正文："Acknowledgments This work was supported by the National Natural Science Foundation of China (81873569, 32030054) ; the National Key R&D Program of China (2018YFC1312700) ; the Chongqing Research Program of Basic Research and Frontier Technology (cstc2020jcyj-zdxmX0007, cstc2020jcyj-msxmX0205) ;Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University [2021] 24; the 111 Project (No. D20028) ."