title: HOXB8 promotes tumor metastasis and the epithelial-mesenchymal transition via ZEB2 targets in gastric cancer.
abstract: OBJECTIVE
  The homeobox B8 (HOXB8) functions as a sequence-specific transcription factor that is involved in development. Increased expression of this gene is associated with a wide variety of tumor; however, its function in gastric cancer has not been clarified. In the present study, the expression of HOXB8 in gastric cancer tissues and influence of HOXB8 on gastric cancer cellular were evaluated.
  
  
  METHODS
  The expression levels of HOXB8 mRNA in human gastric cancer tissues were analyzed through quantitative RT-PCR. To test the role of HOXB8 in gastric cancer metastasis, the cell transwell assay was performed. Microarray, ChIP-qPCR, and Western blot were used to explore the possible mechanism that HOXB8 promotes gastric cancer cells metastasis.
  
  
  RESULTS
  In this study, we found that HOXB8 showed higher expression in metastatic tissues than no-metastatic tissues. Overexpression of HOXB8 can promote gastric cancer cells migration and invasion, while silencing HOXB8 leads to the opposite results. Overexpression of HOXB8 also increases the rate of metastasis in NCI-N87 mice, while silencing HOXB8 has the opposite results. Furthermore, HOXB8 promotes epithelial-mesenchymal transformation of AGS cells. We also found that ZEB2 can interact with HOXB8 and may be a downstream factor of HOXB8 by using microarray. Knockdown of ZEB2 can inhibit HOXB8-induced migration and invasion capacity, as well as the epithelial-mesenchymal transformation in gastric cancer cells.
  
  
  CONCLUSIONS
  The results showed that HOXB8 plays an important role in the development and metastasis of gastric carcinoma.
authors.affiliation: Department of Gastroenterology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
authors.forename: Wen-Jin
authors.initials: WJ
authors.lastname: Ding
authors.affiliation: Department of Diagnosis and Treatment of Digestive Endoscopy, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
authors.forename: Mei-Mei
authors.initials: MM
authors.lastname: Chen
authors.affiliation: Department of Diagnosis and Treatment of Digestive Endoscopy, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China. quchunyingdoc@hotmail.com.
authors.forename: Chun-Ying
authors.initials: CY
authors.lastname: Qu
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009362:Neoplasm Metastasis; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: C490669:HOXB8 protein, human; D018398:Homeodomain Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2
keywords: Epithelial–mesenchymal transition; Gastric cancer; HOXB8; ZEB2