title: Transcriptional control of PAX4-regulated miR-144/451 modulates metastasis by suppressing ADAMs expression.
abstract: Paired box gene 4 (PAX4) is a transcriptional modulator located on chromosome 7q32, and its expression is dysregulated in a variety of human cancers, suggesting that PAX4 may be important in multiple tumors as a driver gene. Here, we show that PAX4 promoted migration and invasion in human epithelial cancers by decreasing miR-144 and miR-451 (miR-144/451) expression levels. Accordingly, miR-144/451 suppressed the migratory and invasive phenotypes, even in PAX4-expressing cells. Mechanistically, miR-144/451 inhibits cancer metastasis by targeting the A disintegrin and metalloproteinase (ADAM) protein family members ADAMTS5 and ADAM10. Their dysregulation is associated with increased tumor invasiveness and metastasis, then reduced patient prognosis in certain epithelial cancers. This discovery suggests that a PAX4-miR-144/451-ADAMs axis regulates human epithelial cancer metastasis, thus opening up therapeutic possibilities and predicting prognosis for those cancer types.
authors.affiliation: Department of Oral and Maxillofacial-Head and Neck Oncology and Faculty of Oral and Maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Oral and Maxillofacial-Head and Neck Oncology and Faculty of Oral and Maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Qin
authors.affiliation: Department of Oral and Maxillofacial-Head and Neck Oncology and Faculty of Oral and Maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Clinical Laboratory, Shanghai Third People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: H
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Oral and Maxillofacial-Head and Neck Oncology and Faculty of Oral and Maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Oral and Maxillofacial-Head and Neck Oncology and Faculty of Oral and Maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: F
authors.initials: F
authors.lastname: Xie
authors.affiliation: 1] Department of Oral and Maxillofacial-Head and Neck Oncology and Faculty of Oral and Maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China [2] Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Oral and Maxillofacial-Head and Neck Oncology and Faculty of Oral and Maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: M
authors.initials: M
authors.lastname: Yan
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.affiliation: 1] Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, China [2] Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Han
authors.affiliation: 1] Department of Oral and Maxillofacial-Head and Neck Oncology and Faculty of Oral and Maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China [2] Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, China.
authors.forename: W
authors.initials: W
authors.lastname: Chen
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D019295:Computational Biology; D019483:Disintegrins / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000473:pathology; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D019483:Disintegrins; D018398:Homeodomain Proteins; C554293:MIRN144 microRNA, human; C531201:MIRN451 microRNA, human; D035683:MicroRNAs; C491709:PAX4 protein, human; D051761:Paired Box Transcription Factors; D051722:ADAM Proteins