Benzo[a]pyrene stimulates miR-650 expression to promote the pathogenesis of fatty liver disease and hepatocellular carcinoma via SOCS3/JAK/STAT3 cascades  

作　　者：Yang Ge Pengfei Gu Wenbo Wang Liyuan Cao Lulu Zhang Jingquan Li Wei Mu Hui Wang 

机构地区：[1]State Key Laboratory of Oncogenes and Related Genes,Center for Single-cell Omics,School of Public Health,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China [2]Department of Oncology,Shanghai Tenth People’s Hospital,School of Medicine,Tongji University,Shanghai 200072,China [3]Institute of Military Health Management,Second Military Medical University,Shanghai 200433,China [4]CAS Key Laboratory of Nutrition,Metabolism and Food Safety,Shanghai Institute of Nutrition and Health,Chinese Academy of Sciences,Shanghai 200031,China

出　　处：《Journal of Molecular Cell Biology》2021年第8期556-564,共9页分子细胞生物学报（英文版）

基　　金：This work was supported by grants from the National Natural Science Foundation of China(82173543,81803269,and 81902939);Shanghai Municipality Health Commission(GWV-10.2-YQ17 and 2019Y0150);Innovative Research Team of High-level Local Universities in Shanghai(YG2017QN68);the Major Science and Technology Innovation Program of Shanghai Municipal Education Commission(2019-01-07-00-01-E00059).

摘　　要：Modern diets,which often feature high levels of fat and charcoal-grilled meat,contribute to the pathogenesis of obesity and non-alcoholic fatty liver disease(NAFLD),resulting in liver cancer progression.Benzo(a)pyrene(B[a]P)is a common environ-mental and foodborne pollutant found in smoke and fire-grilled foods,which can have an adverse effect on human health.Hepatocellular carcinoma(HCC)is the fifth leading cause of cancer and the second leading cause of cancer-related deaths worldwide.The epidemiological studies suggest that both environmental risk factors and chronic liver injury including NAFL are important for HCC development,but the precise mechanisms linking eating habits to hepato-carcinogenesis remain unclear.In the present study,we demonstrated that various miRNAs in B[a]P-exposed tumor cells contribute to tumor metastasis,among which miR-650 could be the most potent inducer.Furthermore,we found that the suppressor of cytokine signaling 3(SOCS3)is directly regulated by miR-650 and its suppression regulates the activation of the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3)cascade.Our findings reveal a possible adverse outcome pathway of SOCS3/JAK/STAT3 regulation in B[a]P-induced HCC progress.These results provide a better understanding of the adverse effects of chronic exposure to B[a]P on human health.

关 键 词：hepatocellular carcinoma microRNAs tumor metastasis S0CS3 prognostic biomarkers 

分 类 号：R735.7[医药卫生—肿瘤]