title: Direct interaction between miR-203 and ZEB2 suppresses epithelial-mesenchymal transition signaling and reduces lung adenocarcinoma chemoresistance.
abstract: miR-203 is a tumor suppressor which participates in the pathogenesis of many tumors including lung adenocarcinoma. However, the role of miR-203 in suppressing chemotherapy resistance to cisplatin (cis-diamminedichloroplatinum; DDP) as well as its molecular mechanism is still to be determined in lung adenocarcinoma. In this study, we found that miR-203 decreased lung cancer cell migration and invasion, and that increased miR-203 expression sensitized lung adenocarcinoma cells to DDP in vitro Furthermore, ZEB2 was found to be a direct target of miR-203, which induces epithelial-mesenchymal transition (EMT) signal. Knock-down of ZEB2 significantly increased DDP chemosensitivity in lung adenocarcinoma. More interestingly, we also demonstrated that ZEB2 could directly bind to E-box of the miR-203 promoter and suppress its expression in lung adenocarcinoma. Our data reveal that miR-203 serves as a negative feedback by directly suppressing the upstream ZEB2 gene, which inhibits EMT signaling and reduces chemoresistance of DDP. Together, these results highlight a feedback loop between miR-203 and ZEB2, which participates in the pathogenesis of lung adenocarcinoma.
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou 510315, China.|Jiu Jiang NO. 1 People's Hospital, Jiujiang 332000, China.
authors.forename: Xunhuang
authors.initials: X
authors.lastname: Duan
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Zhaojian
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Lingyuan
authors.initials: L
authors.lastname: Gao
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou 510315, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou 510315, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Deng
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou 510315, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Luo
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou 510315, China luorc01@163.com fangweiyi1975@163.com.|Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Weiyi
authors.initials: W
authors.lastname: Fang
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou 510315, China luorc01@163.com fangweiyi1975@163.com.
authors.forename: Rongcheng
authors.initials: R
authors.lastname: Luo
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D018398:Homeodomain Proteins; C546703:MIRN203 microRNA, human; D035683:MicroRNAs; D012097:Repressor Proteins; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2
keywords: ZEB2; lung adenocarcinoma; miR-203; tumor suppressor