title: SiRNA-targeted carboxypeptidase D inhibits hepatocellular carcinoma growth.
abstract: Carboxypeptidase D (CPD), a membrane-bound metallocarboxypeptidase that functions as a docking receptor for duck hepatitis B virus, is frequently overexpressed in human cancers. We have explored its expression pattern, clinical significance, and biological function of CPD in hepatocellular carcinoma (HCC). CPD expression was markedly elevated in HCCs relative to adjacent non-tumor liver tissues, as determined by quantitative real-time polymerase chain reaction and Western blot analysis. Immunohistochemistry showed that 164 of 400 (41%) HCCs had high expression of CPD. CPD overexpression was significantly associated with serum levels of hepatitis B surface antigen and hepatitis B e antigen, liver cirrhosis, pathological grade, and intrahepatic metastasis. Knockdown of endogenous CPD expression in Huh7 HCC cells by RNA interference reduced cell proliferation, blocked the cell cycle at G1 phase, and increased apoptosis. Many genes implicated in cell-cycle regulation, including P21waf1, P27 Kip1, SKP2, and CDC2, were deregulated by CPD downregulation. Thus CPD is frequently upregulated in HCC, and targeting CPD inhibits HCC cell proliferation through induction of G1 cell-cycle arrest and apoptosis, thereby providing a potential therapeutic target for this malignancy.
authors.affiliation: The First Department of Surgery, Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, Zhejiang University of Traditional Chinese Medicine, Hangzhou, P.R., China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jin
authors.forename: Jie
authors.initials: J
authors.lastname: Fu
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Feng
authors.forename: Shou-Mei
authors.initials: SM
authors.lastname: Wang
authors.forename: Xue
authors.initials: X
authors.lastname: Huang
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Zhu
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Zhang
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000821:virology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D006509:Hepatitis B / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000378:metabolism; D006513:Hepatitis B e Antigens / Q000235:genetics / Q000378:metabolism; D006515:Hepatitis B virus / Q000502:physiology; D006801:Humans; D008113:Liver Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000821:virology; D011506:Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D011506:Proteins; D034741:RNA, Small Interfering; C094315:metallocarboxypeptidase D
keywords: RNA interference; carboxypeptidase D; cell cycle; hepatoma; therapeutic target