Hypoxia upregulates hepatic angiopoietin-2 transcription to promote the progression of hepatocellular carcinoma  

作　　者：Jun-Ling Yang Jie Yang Rong-Fei Fang Wen-Li Sai Deng-Fu Yao Min Yao 

机构地区：[1]Research Center of Clinical Medicine,Affiliated Hospital of Nantong University and Department of Immunology,Medical School of Nantong University,Nantong 226001,Jiangsu Province,China [2]Department of Biology,Life Science School of Nantong University,Nantong 226009,Jiangsu Province,China [3]Department of Gastroenterology,Affiliated Hospital of Nantong University,Nantong 226001,Jiangsu Province,China

出　　处：《World Journal of Hepatology》2024年第12期1480-1492,共13页世界肝病学杂志（英文）

基　　金：Supported by the National Natural Science Foundation of China,No.32470985 and No.81673241.

摘　　要：BACKGROUND Angiopoietin-2(Ang-2)level is related to hepatocellular carcinoma(HCC)pro-gression.However,the dynamic expression and regulatory mechanism of Ang-2 remain unclear.AIM To investigate Ang-2 levels in chronic liver diseases and validate early monitoring value with a dynamic model in hepatocarcinogenesis.METHODS Sprague-Dawley rats in hepatocarcinogenesis were induced with diet 2-fluo-renylacet-amide,and grouped based on liver histopathology by hematoxylin and eosin staining.Differently expressed genes or Ang-2 mRNA in livers were ana-lyzed by whole-genome microarray.Ang-2 levels in chronic liver diseases were detected by an enzyme-linked immunosorbent assay.RESULTS Clinical observation reveled that the circulating levels of Ang-2 and hypoxia-inducible factor-1α(HIF-1α)in patients with chronic liver diseases were progressively increased from benign to HCC(P<0.001).Dynamic model va-lidated that the up-regulated Ang-2 in liver and blood was positively correlated with HIF-1αin hepatocarcino-genesis(P<0.001).Mechanistically,Ang-2 was regulated by HIF-1α.When specific HIF-1α-microRNAs transfected into HCC cells,the cell proliferation significantly inhibited,HIF-1αand Ang-2 down-regulated,and also affected epithelial-mesenchymal transition via increasing E-cadherin to block cell invasion or migration with reducing of snail,twist and vimentin.CONCLUSION Hypoxia-induced Ang-2 up-regulating expression might serve as a sensitive early monitoring biomarker for hepatocarcinogenesis or HCC metastasis.

关 键 词：ANGIOPOIETIN-2 Hypoxia-inducible factor-1α HEPATOCARCINOGENESIS Dynamic model Metastasis 

分 类 号：R512.62[医药卫生—内科学] R735.7[医药卫生—临床医学]