title: HOXA7 stimulates human hepatocellular carcinoma proliferation through cyclin E1/CDK2.
abstract: HOX genes are transcription factors that control morphogenesis, organogenesis and differentiation. Increasing evidence suggests that HOX genes play a role in hepatocellular carcinoma (HCC) progression; however few studies have defined the functional roles and mechanisms of action. In the present study, we used siRNA and forced-expression in multiple cell lines to define the role of HOXA7 in the regulation of proliferation of HCC in vitro and in vivo. Knockdown of endogenous HOXA7 decreased the proliferation of HepG2 and QGY-7703 cells. These changes were not associated with significant changes in cyclin D1 and CDK4. However, downregulation of HOXA7 significantly reduced cyclin E1 and CDK2 protein levels. Conversely, overexpression of HOXA7 in QSG-7701 cells stimulated proliferation and increased cyclin E1 and CDK2 protein levels. Our results confirmed that HOXA7 promoted cell proliferation, and these changes were mediated by cyclin E1/CDK2. These observations contribute to our understanding of the important roles of HOXA7 in HCC development and progression and HOXA7 could be a promising molecular target for the development of new diagnostic and therapeutic strategies for HCC.
authors.affiliation: Tumor Immunobiology Laboratory of the Cancer Research Institute, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Key Laboratory of Carcinogenesis, Ministry of Health, Central South University, Changsha, Hunan, P.R. China.
authors.forename: Yuehui
authors.initials: Y
authors.lastname: Li
authors.affiliation: Xiangya Third Hospital, Central South University, Changsha, Hunan, P.R. China.
authors.forename: Xiao Hui
authors.initials: XH
authors.lastname: Yang
authors.affiliation: Tumor Immunobiology Laboratory of the Cancer Research Institute, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Key Laboratory of Carcinogenesis, Ministry of Health, Central South University, Changsha, Hunan, P.R. China.
authors.forename: Shu Juang
authors.initials: SJ
authors.lastname: Fang
authors.affiliation: Tumor Immunobiology Laboratory of the Cancer Research Institute, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Key Laboratory of Carcinogenesis, Ministry of Health, Central South University, Changsha, Hunan, P.R. China.
authors.forename: Chang Fei
authors.initials: CF
authors.lastname: Qin
authors.affiliation: Tumor Immunobiology Laboratory of the Cancer Research Institute, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Key Laboratory of Carcinogenesis, Ministry of Health, Central South University, Changsha, Hunan, P.R. China.
authors.forename: Rui Li
authors.initials: RL
authors.lastname: Sun
authors.affiliation: Tumor Immunobiology Laboratory of the Cancer Research Institute, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Key Laboratory of Carcinogenesis, Ministry of Health, Central South University, Changsha, Hunan, P.R. China.
authors.forename: Zhao Yang
authors.initials: ZY
authors.lastname: Liu
authors.affiliation: Tumor Immunobiology Laboratory of the Cancer Research Institute, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Key Laboratory of Carcinogenesis, Ministry of Health, Central South University, Changsha, Hunan, P.R. China.
authors.forename: Bin Yuan
authors.initials: BY
authors.lastname: Jiang
authors.affiliation: Tumor Immunobiology Laboratory of the Cancer Research Institute, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Key Laboratory of Carcinogenesis, Ministry of Health, Central South University, Changsha, Hunan, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wu
authors.affiliation: Tumor Immunobiology Laboratory of the Cancer Research Institute, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Key Laboratory of Carcinogenesis, Ministry of Health, Central South University, Changsha, Hunan, P.R. China.
authors.forename: Guancheng
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism*; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015513:Oncogene Proteins / Q000378:metabolism*; D014162:Transfection
chemical_list: C530104:CCND1 protein, human; C475820:CCNE1 protein, human; D019927:Cyclin E; C115962:HOXA7 protein, human; D018398:Homeodomain Proteins; D015513:Oncogene Proteins; D019938:Cyclin D1; C495900:CDK4 protein, human; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4