title: HOXD10 acts as a tumor-suppressive factor via inhibition of the RHOC/AKT/MAPK pathway in human cholangiocellular carcinoma.
abstract: HOXD10, a key regulator of cell-differentiated phenotype maintainence, has been demonstrated to be involved in the tumorigenesis of many human malignacies. However, the status of HOXD10 expression and its biological function in cholangiocellular carcinoma (CCC) remain to be clarified. In the present study, we investigated the clinical significance and biological functions of HOXD10 in CCC and found that the expression of HOXD10 and its downstream effector RHOC was significantly different in well-differentiated CCC tissues compared with poorly-differentiated lesions. We also observed a significant correlation between low HOXD10 and high RHOC expression levels and worse prognosis. The stable overexpression of HOXD10 by lentivirus vector significantly inhibited cell invasion partly by downregulating the expression of MMP2 and MMP9, and significantly increased early apoptosis in CCC cell lines and induced G1 phase cell cycle arrest, contributing to the inhibition of cell proliferation in vitro. Additionally, we demonstrated that the inactivation of the RHOC/AKT/MAPK pathway was involved in the tumor-suppressive functions of HOXD10 in CCC. These results suggested that HOXD10 may be a putative suppressor gene and can act as a prognostic marker and potentially a novel therapeutic target for CCC.
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710062, P.R. China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Medical Oncology, Xi'an Chest Hospital of Shaanxi, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Jiupeng
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Henan Science and Technology University, Luoyang, Henan 471003, P.R. China.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Mi
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710062, P.R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Ma
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710062, P.R. China.
authors.forename: Yangwei
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710062, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ning
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710062, P.R. China.
authors.forename: Chuying
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710062, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of General Surgery, Tangdu Hospital, Xi'an, Shaanxi 710038, P.R. China.
authors.forename: Huadong
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710062, P.R. China.
authors.forename: Enxiao
authors.initials: E
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D016086:Lentivirus; D008297:Male; D008875:Middle Aged; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D016019:Survival Analysis; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D020741:rho GTP-Binding Proteins / Q000235:genetics*; D000075024:rhoC GTP-Binding Protein
chemical_list: D018398:Homeodomain Proteins; D014157:Transcription Factors; C072064:HOXD10 protein, human; D051057:Proto-Oncogene Proteins c-akt; D020929:Mitogen-Activated Protein Kinase Kinases; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D000075024:rhoC GTP-Binding Protein