title: ShRNA-targeted centromere protein A inhibits hepatocellular carcinoma growth.
abstract: BACKGROUND
  Centromere protein A (CENP-A) plays important roles in cell-cycle regulation and genetic stability. Herein, we aimed to investigate its expression pattern, clinical significance, and biological function in hepatocellular carcinoma (HCC).
  
  
  RESULTS
  CENP-A expression at the mRNA and protein levels was examined in 20 pairs of fresh HCCs and corresponding nontumor liver tissues. Immunohistochemistry for CENP-A was performed on 80 paraffin-embedded HCC specimens, and the clinical significance of its expression was analyzed. A human HCC cell line HepG2 with high abundance of CENP-A was used to study the effects of manipulating CENP-A on HCC growth. Quantitative real-time polymerase chain reaction arrays and Western blot analysis were employed to identify the cell-cycle control- and apoptosis-related genes regulated by CENP-A. The results showed that CENP-A was aberrantly overexpressed in HCCs relative to adjacent nontumor tissues. This overexpression was significantly associated with positive serum HBsAg status, increased histological grade, high Ki-67 index and P53 immunopositivity. Knockdown of CENP-A in HepG2 cells reduced cell proliferation, blocked cell cycle at the G1 phase, and increased apoptosis. The antiproliferative effects of CENP-A silencing were also observed in vivo. Conversely, CENP-A overexpression promoted HCC cell growth and reduced apoptosis. Furthermore, many genes implicated in cell-cycle regulation and apoptosis, including CHK2, P21waf1, P27 Kip1, SKP2, cyclin G1, MDM2, Bcl-2, and Bax, were deregulated by manipulating CENP-A.
  
  
  CONCLUSIONS
  Overexpression of CENP-A is frequently observed in HCC. Targeting CENP-A can inhibit HCC growth, likely through the regulation of a large number genes involved in cell-cycle progression and apoptosis, and thereby represents a potential therapeutic strategy for this malignancy.
authors.affiliation: Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Li
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhu
authors.forename: Shuhui
authors.initials: S
authors.lastname: Zhang
authors.forename: Danghui
authors.initials: D
authors.lastname: Yu
authors.forename: Hongyu
authors.initials: H
authors.lastname: Yu
authors.forename: Lina
authors.initials: L
authors.lastname: Liu
authors.forename: Xiaozhe
authors.initials: X
authors.lastname: Cao
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Hengjun
authors.initials: H
authors.lastname: Gao
authors.forename: Minghua
authors.initials: M
authors.lastname: Zhu
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D034741:RNA, Small Interfering / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D001324:Autoantigens; C000619700:CENPA protein, human; C000619701:Cenpa protein, mouse; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; D034741:RNA, Small Interfering