title: TGF-β-miR-34a-CCL22 signaling-induced Treg cell recruitment promotes venous metastases of HBV-positive hepatocellular carcinoma.
abstract: Portal vein tumor thrombus (PVTT) is strongly correlated to a poor prognosis for patients with hepatocellular carcinoma (HCC). In this study, we uncovered a causative link between hepatitis B virus (HBV) infection and development of PVTT. Mechanistically, elevated TGF-β activity, associated with the persistent presence of HBV in the liver tissue, suppresses the expression of microRNA-34a, leading to enhanced production of chemokine CCL22, which recruits regulatory T (Treg) cells to facilitate immune escape. These findings strongly suggest that HBV infection and activity of the TGF-β-miR-34a-CCL22 axis serve as potent etiological factors to predispose HCC patients for the development of PVTT, possibly through the creation of an immune-subversive microenvironment to favor colonization of disseminated HCC cells in the portal venous system.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Yang
authors.forename: Qi-Jing
authors.initials: QJ
authors.lastname: Li
authors.forename: Yuxiong
authors.initials: Y
authors.lastname: Feng
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Markowitz
authors.forename: Shanglei
authors.initials: S
authors.lastname: Ning
authors.forename: Yuezhen
authors.initials: Y
authors.lastname: Deng
authors.forename: Jiangsha
authors.initials: J
authors.lastname: Zhao
authors.forename: Shan
authors.initials: S
authors.lastname: Jiang
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Yuan
authors.forename: Hong-Yang
authors.initials: HY
authors.lastname: Wang
authors.forename: Shu-Qun
authors.initials: SQ
authors.lastname: Cheng
authors.forename: Dong
authors.initials: D
authors.lastname: Xie
authors.forename: Xiao-Fan
authors.initials: XF
authors.lastname: Wang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000473:pathology / Q000556:secondary* / Q000821:virology; D045744:Cell Line, Tumor; D054422:Chemokine CCL22 / Q000378:metabolism*; D005260:Female; D006509:Hepatitis B / Q000150:complications*; D006515:Hepatitis B virus / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000276:immunology / Q000473:pathology* / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis / Q000378:metabolism*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011169:Portal Vein; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D059016:Tumor Microenvironment
chemical_list: C515482:CCL22 protein, human; D054422:Chemokine CCL22; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D016212:Transforming Growth Factor beta