title: BCL-3 promotes the tumor growth of hepatocellular carcinoma by regulating cell proliferation and the cell cycle through cyclin D1.
abstract: Previous studies have demonstrated the aberrant expression and oncogenic role of B-cell CLL/lymphoma-3 (BCL-3) in human malignancies. However, the clinical significance of BCL-3 and its biological function in human hepatocellular carcinoma (HCC) remain unknown. In the present study, the expression levels of BCL-3 protein and mRNA in 90 pairs of HCC and matched non-tumor tissues were analyzed using immunohistochemistry and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). We found that the expression levels of BCL-3 protein and mRNA in HCC tissues were significantly higher than those in the matched tumor-adjacent tissues. In addition, positive expression of BCL-3 was associated with adverse clinicopathological characteristics of the HCC patients including hepatitis B virus (HBV) infection, tumor size, cirrhosis and advanced tumor-node-metastasis (TNM) stage. Moreover, HCC patients with positive expression of BCL-3 had significantly decreased 5-year overall survival and recurrence-free survival. Importantly, BCL-3 expression was an independent prognostic factor for indicating the survival of the HCC patients. Functionally, BCL-3 knockdown markedly inhibited cell viability, proliferation and cell cycle progression in HepG2 cells, while BCL-3 overexpression promoted these cellular processes in Huh7 cells. Accordingly, in vivo experiments indicated that BCL-3 knockdown prominently suppressed the tumor growth of HepG2 cells in nude mice. Mechanistically, we revealed that the expression of cyclin D1 was decreased after BCL-3 knockdown in the HepG2 cells and was increased after BCL-3 overexpression in the Huh7 cells. Cyclin D1 silencing was found to abrogate the functional effects of BCL-3 on cellular processes in Huh7 cells. Taken together, our data suggest that BCL-3 may serve as a promising biomarker and an effective therapeutic target of HCC.
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Kangsheng
authors.initials: K
authors.lastname: Tu
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Zhikui
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Bowen
authors.initials: B
authors.lastname: Yao
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yumo
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Changwei
authors.initials: C
authors.lastname: Dou
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Guozhi
authors.initials: G
authors.lastname: Yin
authors.affiliation: Department of Emergency, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D000081242:B-Cell Lymphoma 3 Protein; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006509:Hepatitis B / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; C000631345:Bcl3 protein, mouse; C530104:CCND1 protein, human; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D019938:Cyclin D1