title: HOXD9 promotes epithelial-mesenchymal transition and cancer metastasis by ZEB1 regulation in hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is a common malignant tumor that severely threatens human health. The poor prognosis of HCC is mainly attributed to intrahepatic and extrahepatic metastases. HOXD9 proteins belong to a superfamily that regulates the development and control of many cellular processes, including proliferation, apoptosis, cell shape, and cell migration. HOXD9 can also function as an oncogene in several cancer cells. However, its biological function in human HCC requires further investigation. In this study, HOXD9 exhibited high expression in invasive HCC cells. HOXD9 overexpression can significantly enhance HCC cell migration, invasion, and metastasis, whereas silencing HOXD9 inhibits these processes. HOXD9 also promotes the epithelial-mesenchymal transition (EMT) of HCC cells. Microarray analysis suggests that ZEB1 can function as a downstream factor of HOXD9. HOXD9 can interact with the promoter region of ZEB1 and promotes ZEB1 expression. ZEB1 knockdown inhibits HOXD9-induced migration and invasion, as well as EMT in HCC cells. This study helps elucidates the oncogenic functions of HOXD9 in HCC.
authors.affiliation: Department of Radiation Oncology, First Affiliated Hospital, Dalian Medical University, Dalian, 116001, China. ttsdoc@126.com.
authors.forename: Xiupeng
authors.initials: X
authors.lastname: Lv
authors.affiliation: Department of the 4th Internal Medical, Liaoning Cancer Hospital & Institute, Shenyang, 110042, China. lifangyidoc@163.com.
authors.forename: Linlin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pathology, Second Affiliated Hospital of Dalian Medical University, Dalian, 116027, China. zyltg2013@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Lv
authors.affiliation: Department of Second Neurology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116001, China. snldoc@163.com.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Qu
authors.affiliation: Department of Laparoscopic Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, 116001, China. jinshidoc@163.com.
authors.forename: Shi
authors.initials: S
authors.lastname: Jin
authors.affiliation: Department of Laparoscopic Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, 116001, China. zhiqhutg@126.com.
authors.forename: Kejun
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, First Affiliated Hospital of Dalian Medical University, Dalian, 116001, China. guangyingqitg@163.com.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Deng
authors.affiliation: Department of Laparoscopic Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, 116001, China. chengleidoc@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Laparoscopic Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, 116001, China. hehuidoc@yeah.net.
authors.forename: Hui
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Laparoscopic Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, 116001, China. dlleidong@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Dong
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D016000:Cluster Analysis; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics*; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: C088822:HOXD9 protein, human; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1