title: CD109 Mediates Cell Survival in Hepatocellular Carcinoma Cells.
abstract: Hepatocellular carcinoma (HCC) accounts for 75-80 % of primary liver cancer, and usually arises after years of liver disease. Thus it is important to understand the molecular mechanisms which drive or mediate the development of HCC.
  
  
  
  In this work, we examined whether CD109 was associated with a poor prognosis in HCC and explored possible underlying mechanisms.
  
  
  
  We examined the CD109 and Ki67 expression levels in 97 patients with HCC using immunohistochemistry. CD109 levels in HCC cells were down-regulated by shRNA transfection. The cycle progression and cell proliferation status of HCC cells were evaluated by flow cytometry and CCK-8 assay. The effect of CD109 on proliferation and apoptosis was investigated by western blot and TUNEL activity assays.
  
  
  
  The CD109 protein was up-regulated in HCC tissue compared with adjacent noncancerous tissue. CD109 expression levels in the 97 patients with HCC were positively correlated with histological grade. Univariate and multivariate survival analysis revealed that CD109 was a significant predictor of overall survival among HCC patients. CD109 shRNA knockdown delayed the G1-S phase transition, abrogated cell proliferation, and increased cell apoptosis. Furthermore, CD109 impaired TGF-β/Smad signaling through control of p-smad2.
  
  
  
  CD109 promoted HCC proliferation and predicted poor prognosis. In addition, CD109 expression was associated with anti-apoptosis in HCC cells.
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China.
authors.forename: Guijuan
authors.initials: G
authors.lastname: Zong
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Department of Immunology, Medical College, Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China.|Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai, Miyagi, 981-8558, Japan.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China.
authors.forename: Shusen
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Department of Immunology, Medical College, Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China.
authors.forename: Yifen
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Department of Immunology, Medical College, Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China.
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Qiu
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Department of Immunology, Medical College, Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China.
authors.forename: Guizhou
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China.
authors.forename: Song
authors.initials: S
authors.lastname: He
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Department of Immunology, Medical College, Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China. taotao201504@163.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Tao
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China. nantong201504@163.com.
authors.forename: Xudong
authors.initials: X
authors.lastname: Chen
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle; D049109:Cell Proliferation / Q000235:genetics*; D002470:Cell Survival; D005260:Female; D005434:Flow Cytometry; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059807:S Phase Cell Cycle Checkpoints / Q000235:genetics; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C120523:CD109 protein, human; D058851:GPI-Linked Proteins; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D018809:Proliferating Cell Nuclear Antigen; D034741:RNA, Small Interfering; C497782:SMAD2 protein, human; D051785:Smad Proteins; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta; C413374:p27 antigen; C505407:CASP3 protein, human; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8
keywords: Apoptosis; CD109; HCC; Prognosis; Proliferation