Human hepatocyte-enriched miRNA-192-3p promotes HBV replication through inhibiting Akt/mTOR signalling by targeting ZNF143 in hepatic cell lines

作者全名："Li, Fahong; Deng, Yingying; Zhang, Shenyan; Zhu, Beidi; Wang, Jun; Wang, Jinyu; Wang, Xueyu; Zhao, Zhenyu; Deng, Wanyu; Mao, Richeng; Shen, Zhongliang; Chen, Jieliang; Broering, Ruth; Lin, Yong; Lu, Mengji; Zhang, Jiming"

作者地址："[Li, Fahong; Zhang, Shenyan; Zhu, Beidi; Wang, Jun; Wang, Jinyu; Mao, Richeng; Shen, Zhongliang; Zhang, Jiming] Fudan Univ, Huashan Hosp, Natl Med Ctr Infect Dis,Shanghai Key Lab Infect D, Shanghai Inst Infect Dis & Biosecur,Dept Infect D, Shanghai, Peoples R China; [Li, Fahong; Wang, Xueyu; Lin, Yong; Lu, Mengji] Univ Duisburg Essen, Univ Hosp Essen, Inst Virol, Hufelandstr 55, D-45122 Essen, Germany; [Deng, Yingying; Zhao, Zhenyu; Lin, Yong] Chongqing Med Univ, Key Lab Mol Biol Infect Dis, Chinese Minist Educ, Chongqing, Peoples R China; [Deng, Wanyu] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Biliary Pancreat Surg, Guangzhou, Guangdong, Peoples R China; [Chen, Jieliang; Zhang, Jiming] Fudan Univ, Shanghai Med Coll, Key Lab Med Mol Virol MOE MOH, Shanghai, Peoples R China; [Broering, Ruth] Univ Duisburg Essen, Univ Hosp Essen, Dept Gastroenterol & Hepatol, Essen, Germany; [Zhang, Jiming] Fudan Univ, Huashan Hosp, Dept Infect Dis, JingAn Branch, Shanghai, Peoples R China"

通信作者："Lu, MJ (通讯作者)，Univ Duisburg Essen, Univ Hosp Essen, Inst Virol, Hufelandstr 55, D-45122 Essen, Germany.; Zhang, JM (通讯作者)，Fudan Univ, Huashan Hosp, Dept Infect Dis, 12 Middle Wulumuqi Rd, Shanghai 200040, Peoples R China.; Lin, Y (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Chinese Minist Educ,Dept Infect Dis,Key Lab Mol B, Chongqing 400016, Peoples R China."

来源：EMERGING MICROBES & INFECTIONS

ESI学科分类：MICROBIOLOGY

WOS号：WOS:000758715100001

JCR分区：Q1

影响因子：13.2

年份：2022

卷号：11

期号：1

开始页：616

结束页：628

文献类型：Article

关键词：MiRNA profile; miR-192-3p; hepatitis B virus; ZNF143; Akt; mTOR signalling; Abbreviations; CMIA; chemiluminescent microparticle immunoassay; HBV; hepatitis B virus; HSC; hepatic stellate cell; KC; Kupffer cell; LSEC; liver sinusoidal endothelial cell; pgRNA; pregenomic RNA; PHH; primary human hepatocyte; RI; replicative intermediate

摘要："Previous studies have revealed multiple tissue- or cell-specific or enriched miRNA profiles. However, miRNA profiles enriched in hepatic cell types and their effect on HBV replication have not been well elucidated. In this study, primary human hepatocytes (PHHs), Kupffer cells (KCs), liver sinusoidal endothelial cells (LSECs), and hepatic stellate cells (HSCs) were prepared from liver specimens of non-HBV-infected patients. Four hepatic cell type-enriched miRNA profiles were identified from purified liver cells miRNA microarray assay. The results revealed that 12 miRNAs, including miR-122-5p and miR-192-3p were PHH-enriched; 9 miRNAs, including miR-142-5p and miR-155-5p were KC-enriched; 6 miRNAs, including miR-126-3p and miR-222-3p were LSEC-enriched; and 14 miRNAs, including miR-214-3p and miR-199a-3p were HSC-enriched. By testing the effect of 11 PHH-enriched miRNAs on HBV production, we observed that miR-192-3p had the greatest pro-virus effect in hepatic cell lines. Moreover, we further found that miR-192-3p promoted HBV replication and gene expression through inhibiting Akt/mTOR signalling by direct targeting of ZNF143 in HepG2.2.15 cells. Additionally, the serum and hepatic miR-192-3p expression levels were significantly higher in chronic hepatitis B patients than in healthy controls and serum miR-192-3p positively correlated with the serum levels of HBV DNA and HBsAg. Collectively, we identified miRNA profiles enriched in four hepatic cell types and revealed that PHH-enriched miR-192-3p promoted HBV replication through inhibiting Akt/mTOR signalling by direct targeting of ZNF143 in hepatic cell lines. Our study provides a specific perspective for the role of hepatic cell type-enriched miRNA in interaction with viral replication and various liver pathogenesis."

基金机构："National Natural Science Foundation of China [81871640, 82172255, 81800526, 82002131, 81801999]; Shanghai Shen Kang Hospital Development Center [SHDC12019116]; Shanghai Key Clinical Specialty Construction Program [ZK2019B24]; Shang Rao Science and Technology Department [2020D001]; Medizinische Fakultat Universitat Duisburg Essen"

基金资助正文："This work was supported by the National Natural Science Foundation of China (81871640, 82172255, 81800526, 82002131, 81801999), the Shanghai Shen Kang Hospital Development Center (SHDC12019116), the Shanghai Key Clinical Specialty Construction Program (ZK2019B24), and Shang Rao Science and Technology Department (2020D001). F.L. received a scholarship from the Medizinische Fakultat Universitat Duisburg Essen."