PIWIL1 governs the crosstalk of cancer cell metabolism and immunosuppressive microenvironment in hepatocellular carcinoma  

作　　者：Ning Wang Hor-Yue Tan Yuanjun Lu Yau-Tuen Chan Di Wang Wei Guo Yu Xu Cheng Zhang Feiyu Chen Guoyi Tang Yibin Feng 

机构地区：[1]School of Chinese Medicine,Li Ka Shing Faculty of Medicine,The University of Hong Kong,Hong Kong SAR,People's Republic of China [2]School of Life Sciences,Jilin University,Changchun City,Jilin Province,People's Republic of China

出　　处：《Signal Transduction and Targeted Therapy》2021年第3期1033-1045,共13页信号转导与靶向治疗（英文）

基　　金：supported by the Research Council of the University of Hong Kong(project codes:104004092 and 104004460);the Wong’s donation(project code:200006276);a donation from the Gaia Family Trust of New Zealand(project code:200007008);the Research Grants Committee(RGC)of Hong Kong,HKSAR(Project Codes:740608,766211,17152116,and 17121419);Enhanced new staff startup fund(Project code:204610519);868Preemptive retention fund(Project code:202007002);Health and Medical Research Fund(Project code:15162961,16172751).

摘　　要：Altered energy metabolism of cancer cells shapes the immune cell response in the tumor microenvironment that faclitates tumorprogression.Herein,we reported the novel of tumor cell-expressed Piwi Like RNA-Mediated Gene Silencing 1(PWL1)in mediatingthe crosstlk of fatty acid metabolism and immune response of human hepatocellular carcinoma(HCC).PlWIL1 expression in HCCwas increased compared to normal hepatic tissues and was positively correlated with the proliferation rate of HCC cell ines.PIWL1overexpression accelerated in vitro proliferation and in vivo growth of HCC tumors,while PIWL1 knockdown showed opositeeffects.PIWL1 increased oxygen consumption and energy production via fatty acid metabolism without altering aerobic glycolysis.lnhibition of fatty acid metablism abolished PWIL1-induced HCC prolferation and growth.RNA-seq analysis revealed that immunesystem regulation might be involved,which was echoed by the experimental observation that PIWL1-overexpressing HCC cellsattracted myeloid-derived suppressor cells(MDSCs)into the tumor microenvironment.MDSCs depletion reduced the prolferationand growth of PlWIL1-overexpressing HCC tumors.Complement C3,whose secretion was induced by PIWL1 in HCC cells,mediatesthe interaction of HCC cells with MDSCs by activated p38 MAPK signaling in MDSCs,which in turn initiated expression of immunosuppressive cytokine L10.Neutralizing lL10 secretion reduced the immunosuppressive activity of MDSCs in the microenvironment of PIWL1-overexpressing HCC.Taken together,our study unraveled the critical role of PIWL1 in initiating theinteraction of cancer cell metabolism and immune cell response in HCC.Tumor cell-expressed PlIWL1 may be a potential target forthe devellopment of novel HCC treatment.

关 键 词：METABOLISM MICROENVIRONMENT HEPATOCELLULAR 

分 类 号：R735.7[医药卫生—肿瘤]