title: The DNA damage repair protein Ku70 regulates tumor cell and hepatic carcinogenesis by interacting with FOXO4.
abstract: The capability for DNA double-strand breaks (DSBs) repair is crucial for chromatin dramatic changes and DNA damage in normal and tumor cells. We have investigated the clinicopathological significance of DNA repair gene Ku70 expression in hepatocellular carcinoma. We demonstrated that Ku70 expression was significantly increased in HCC, and the high expression levels were significantly correlated with gender, maximal tumor size, HBsAg status, tumor nodule number, distant metastasis and Ki-67 expression by clinicopathological analysis. The Kaplan-Meier survival curves revealed that increasing Ku70 expression was associated with poor prognosis in HCC patients. Ku70 expression was an independent prognostic marker of overall HCC patient survival in a multivariate analysis. In addition, through serum starvation and refeeding, we found that Ku70 was lowly expressed in serum-starved Huh7 and HepG2 HCC cells, and was progressively increased after serum-additioning. Furthermore, knockdown of Ku70 inhibited cell proliferation accompanying an increase in p27(kip1) levels through interacting with FOXO4. These findings provide a rational framework for the progression of HCC and could be a potential molecular therapy by targeting the Ku70-FOXO4 interaction.
authors.affiliation: Department of Digestion, Affiliated Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Oncology, The Second Peoples Hospital of Nantong, Nantong, Jiangsu 226001, People's Republic of China.
authors.forename: Xiubing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Oncology, The Second Peoples Hospital of Nantong, Nantong, Jiangsu 226001, People's Republic of China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Oncology, The Second Peoples Hospital of Nantong, Nantong, Jiangsu 226001, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Oncology, The Second Peoples Hospital of Nantong, Nantong, Jiangsu 226001, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Digestion, Affiliated Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
authors.forename: Shusen
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Digestion, Affiliated Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
authors.forename: Runzhou
authors.initials: R
authors.lastname: Ni
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D063646:Carcinogenesis / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality; D018797:Cell Cycle Proteins; D004249:DNA Damage / Q000502:physiology; D004260:DNA Repair / Q000502:physiology; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D053208:Kaplan-Meier Estimate; D000072200:Ku Autoantigen / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C108803:FOXO4 protein, human; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; D000072200:Ku Autoantigen
keywords: Cell proliferation; FOXO4; Hepatocellular carcinoma; Ku70; p27(kip1)