title: Expression and Clinical Role of Cdc5L as a Novel Cell Cycle Protein in Hepatocellular Carcinoma.
abstract: BACKGROUND
  Cell division cycle 5-like (Cdc5L), as a pre-mRNA splicing factor, is a regulator of mitotic progression. Previous study found that deletion of endogenous Cdc5L decreases the cell viability via dramatic mitotic arrest, while the role of Cdc5L in cancer biology remains under debate.
  
  
  OBJECTIVE
  To investigate the involvement of Cdc5L in the progression of hepatocellular carcinoma (HCC).
  
  
  METHODS
  In this study, the expression of Cdc5L was evaluated by Western blot in 8 paired fresh HCC tissues and immunohistochemistry on 116 paraffin-embedded slices. We treated HCC cells by nocodazole to analyze the role of Cdc5L in mitotic progress. To determine whether Cdc5L could regulate the proliferation of HCC cells, we increased endogenous Cdc5L and analyzed the proliferation of HCC cells using Western blot, CCK8, flow cytometry assays, and colony formation analyses. Furthermore, Cdc5L-siRNA oligos were used to confirm that Cdc5L plays an essential role in HCC development.
  
  
  RESULTS
  Cdc5L was highly expressed in HCC and significantly associated with multiple clinicopathological factors, including AJCC stage, tumor size, and Ki-67. Besides, univariate and multivariate survival analyses demonstrated that high Cdc5L expression was an independent prognostic factor for HCC patients' poor survival. Overexpression of Cdc5L favors cell cycle progress of HCC cells, while downregulation of Cdc5L results in cell cycle arrest at G2/M phase and reduced cell proliferation of HCC cells.
  
  
  CONCLUSIONS
  Our findings suggested that Cdc5L could play an important role in the tumorigenesis of HCC and thus be a potential therapeutical target to prevent HCC progression.
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu Province, People's Republic of China.
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Qiu
authors.affiliation: Department of Medical Oncology, Second Peoples Hospital of Nantong, 43 Xinglong Road, Nantong, 226001, Jiangsu Province, People's Republic of China.
authors.forename: Xiubing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu Province, People's Republic of China.
authors.forename: Wenkai
authors.initials: W
authors.lastname: Ni
authors.affiliation: Department of Medical Oncology, Second Peoples Hospital of Nantong, 43 Xinglong Road, Nantong, 226001, Jiangsu Province, People's Republic of China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Medical Oncology, Second Peoples Hospital of Nantong, 43 Xinglong Road, Nantong, 226001, Jiangsu Province, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Medical Oncology, Second Peoples Hospital of Nantong, 43 Xinglong Road, Nantong, 226001, Jiangsu Province, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Medical Oncology, Second Peoples Hospital of Nantong, 43 Xinglong Road, Nantong, 226001, Jiangsu Province, People's Republic of China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu Province, People's Republic of China. nrz1234@yeah.net.
authors.forename: Runzhou
authors.initials: R
authors.lastname: Ni
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong, 226001, Jiangsu Province, People's Republic of China. tao1234tao@yeah.net.
authors.forename: Tao
authors.initials: T
authors.lastname: Tao
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation / Q000235:genetics*; D002470:Cell Survival; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D047368:Tumor Burden; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C508357:CDC5L protein, human; D018797:Cell Cycle Proteins; D019394:Ki-67 Antigen; D016601:RNA-Binding Proteins
keywords: Cdc5L; HCC; Mitotic progression; Prognostic factor; Tumorigenesis