title: HPV-16 E6 promotes cell growth of esophageal cancer via downregulation of miR-125b and activation of Wnt/β-catenin signaling pathway.
abstract: High-risk human papillomavirus (HPV) is a possible cause of esophageal cancer. However, the molecular pathogenesis of HPV-infected esophageal cancer remains unclear. The expression levels of some microRNAs including miR-125b have been negatively correlated with HPV infection, and miR-125b downregulation is associated with tumorigenesis. In addition, Wnt/β-catenin signaling pathway has been suggested to play an important role in esophageal cancer (EC). We examined miR-125b and Wnt/β-catenin signaling pathway in HPV-16 E6 promoted tumor progression in EC. HPV-16 E6 transfection decreased markedly the expression levels of miR-125b and promoted the colony formation in the Eca 109 and Kyse 150 cell lines, and restoration of miR-125b expression level antagonized the increased colony formation in HPV-16 E6 transfected cell lines. We also demonstrated that overexpression of E6 upregulated the Wnt/β-catenin signaling activity via modulating the multiple regulators including TLE1, GSK3β, and sFRP4. Overexpression of miR-125b restored the expression levels of these proteins. Expression of miR-125b was lower in HPV-16 E6 positive esophageal cancer tissues, and was negatively correlated with E6 mRNA levels. Our results indicate that HPV-16 E6 promotes tumorigenesis in EC via down-regulation of miR-125b, and this underlying mechanism may be involved in the activation of the Wnt/β-catenin signaling pathway.
authors.affiliation: Department of Cardiothoracic Surgery, The First Affiliated Hospital of Soochow University Suzhou 215006, Jiangsu, China ; Department of Thoracic Sugery, Huai'an First People's Hospital, Nanjing Medical University Huai'an 223300, Jiangsu, China.
authors.forename: Bao
authors.initials: B
authors.lastname: Zang
authors.affiliation: Department of Cardiothoracic Surgery, The First Affiliated Hospital of Soochow University Suzhou 215006, Jiangsu, China ; Department of Thoracic Surgery, Second Affiliated Hospital of Southeast University Jiangsu 210003, China.
authors.forename: Guojin
authors.initials: G
authors.lastname: Huang
authors.affiliation: Department of Thoracic Sugery, Huai'an First People's Hospital, Nanjing Medical University Huai'an 223300, Jiangsu, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cardiothoracic Surgery, The First Affiliated Hospital of Soochow University Suzhou 215006, Jiangsu, China.
authors.forename: Shiying
authors.initials: S
authors.lastname: Zheng
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000473:pathology* / Q000821:virology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D000071679:Glycogen Synthase Kinase 3 beta / Q000235:genetics / Q000378:metabolism; D052162:Human papillomavirus 16 / Q000502:physiology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D030361:Papillomavirus Infections / Q000473:pathology* / Q000821:virology; D012097:Repressor Proteins / Q000235:genetics*; D015854:Up-Regulation; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C068651:E6 protein, Human papillomavirus type 16; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta
keywords: HPV-16 E6; Wnt/β-catenin; esophageal cancer; miR-125b