title: A directly negative interaction of miR-203 and ZEB2 modulates tumor stemness and chemotherapy resistance in nasopharyngeal carcinoma.
abstract: miR-203 is a tumor suppressor that is disregulated in numerous malignancies including nasopharyngeal carcinoma (NPC). However, the role of miR-203 in suppressing tumor stemness, chemotherapy resistance as well as its molecular mechanisms are unclear. In this study, we observed that miR-203 suppressed cell migration, invasion, tumor stemness, and chemotherapy resistance to cisplatin (DDP) in vitro and in vivo. miR-203 exerted these effects by targeting ZEB2 and downstream epithelial-mesenchymal transition (EMT) and tumor stemness signals. Interestingly we observed that miR-203 expression was directly suppressed by ZEB2 via targeting its promoter, which significantly reduced cell migration, invasion, tumor stemness, and chemotherapy resistance in NPC cells. Finally, we found that miR-203 was negatively correlated with ZEB2 expression in NPC tissues and tumor spheres. Our data demonstrate a directly negative feedback loop between miR-203 and ZEB2 participating in tumor stemness and chemotherapy resistance, highlighting the therapeutic potential of targeting this signal for NPC chemotherapy.
authors: Department of Pathology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China.
authors: Qingping
authors: Q
authors: Jiang
authors: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.|Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, Guangdong 510315, China.
authors: Ying
authors: Y
authors: Zhou
authors: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.|Sino-American Cancer Research Institute, Guangdong Medical College, Dongguan 523808, China.
authors: Huiling
authors: H
authors: Yang
authors: Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, Guangdong 510315, China.
authors: Libo
authors: L
authors: Li
authors: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors: Xiaojie
authors: X
authors: Deng
authors: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors: Chao
authors: C
authors: Cheng
authors: Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, Guangdong 510315, China.
authors: Yingying
authors: Y
authors: Xie
authors: Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, Guangdong 510315, China.
authors: Xiaojun
authors: X
authors: Luo
authors: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.|Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, Guangdong 510315, China.
authors: Weiyi
authors: W
authors: Fang
authors: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.|Department of Pathology, Medical University of Guangzhou, Guangzhou 510182, China.
authors: Zhen
authors: Z
authors: Liu
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D064593:Heterografts; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000473:pathology*; D000074165:Zinc Finger E-box Binding Homeobox 2 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C546703:MIRN203 microRNA, human; D035683:MicroRNAs; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2
keywords: NPC; ZEB2; chemotherapy resistance; miR-203a; tumor stemness