title: The histone acetyltransferase hMOF suppresses hepatocellular carcinoma growth.
abstract: Males absent on the first (MOF) is a histone acetyltransferase belongs to the MYST (MOZ, Ybf2/Sas3, Sas2 and TIP60) family. In mammals, MOF plays critical roles in transcription activation by acetylating histone H4K16, a prevalent mark associated with chromatin decondensation. MOF can also acetylate transcription factor p53 on K120, which is important for activation of pro-apoptotic genes; and TIP5, the largest subunit of NoRC, on K633. However, the role of hMOF in hepatocellular carcinoma remains unknown. Here we find that the expression of hMOF is significantly down-regulated in human hepatocellular carcinoma and cell lines. Furthermore, our survival analysis indicates that low hMOF expression predicts poor overall and disease-free survival. We demonstrate that hMOF knockdown promotes hepatocellular carcinoma growth in vitro and in vivo, while hMOF overexpression reduces hepatocellular carcinoma growth in vitro and in vivo. Mechanically, we show that hMOF regulates the expression of SIRT6 and its downstream genes. In summary, our findings demonstrate that hMOF participates in human hepatocellular carcinoma by targeting SIRT6, and hMOF activators may serve as potential drug candidates for hepatocellular carcinoma therapy.
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Infectious Disease Control and Prevention, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Pan
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Huang
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Zhou
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China. Electronic address: Zeyapa@sohu.com.
authors.forename: Ze-Ya
authors.initials: ZY
authors.lastname: Pan
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D051548:Histone Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D051379:Mice; D009368:Neoplasm Transplantation; D015398:Signal Transduction; D037761:Sirtuins / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis; D047368:Tumor Burden
chemical_list: D051548:Histone Acetyltransferases; C496552:KAT8 protein, human; C516592:SIRT6 protein, human; D037761:Sirtuins
keywords: Hepatocellular carcinoma; SIRT6; hMOF