A Transforming Growth Factor-β and H19 Signaling Axis in Tumor-Initiating Hepatocytes That Regulates Hepatic Carcinogenesis

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Jinqiang ZhangTong Wu

Abstract

Functions of transforming growth factor-β (TGF-β) in the liver vary depending on specific cell types and their temporal response to TGF-β during different stages of hepatocarcinogenesis (HCG). Through analysis of tumor tissues from hepatocellular carcinoma (HCC) patients, we were able to cluster hepatic epithelial cell-derived TGF-β gene signatures in association with distinct clinical prognoses. To delineate the role of hepatic epithelial TGF-β signaling in HCC development, we used an experimental system in which tumor-initiating hepatocytes (TICs) were isolated from TGF-β receptor II floxed mice (Tgfbr2fl/fl ) and transplanted into syngeneic C57BL/6J mice by splenic injection. Recipient mice were then administered Cre-expressing adenovirus (Ad-Cre) to inactivate Tgfbr2 in transplanted TICs. After latency, Tgfbr2-inactivated TICs formed larger and more tumor nodules in recipient livers compared to TICs without Tgfbr2 inactivation. In vitro analyses revealed that treatment of cultured TICs with TGF-β inhibited expression of progenitor cell factors (including SRY (sex determining region Y)-box 2 [Sox2]). RNA sequencing (RNA-seq) analysis identified H19 as one of the most up-regulated long noncoding RNA (lncRNA) in association wi...Continue Reading

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Citations

Jun 3, 2020·Cancer Science·Panagiotis Papoutsoglou, Aristidis Moustakas
Jan 4, 2020·Oncology Letters·Ji WangFen Yang
Dec 15, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Shuyun Rao, Lopa Mishra
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Jun 25, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Chenqi WangYuhui Zang
Nov 2, 2020·Cancer Letters·Chen XieJin-E Yang
Feb 19, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Junya NingJinpu Yu
Nov 24, 2020·Translational Research : the Journal of Laboratory and Clinical Medicine·Zhihong YangSuthat Liangpunsakul
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Aug 5, 2021·Cell & Bioscience·Wenhua SuHong Zhang
May 27, 2020·Experimental and Molecular Pathology·Xiaojiaoyang Li, Runping Liu
Feb 26, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yanyan WangHuiping Zhou
Sep 11, 2021·Nature Reviews. Gastroenterology & Hepatology·Terence Kin-Wah LeeStephanie Ma
Nov 4, 2021·Hepatology Communications·Romain DesertNatalia Nieto

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