A directly negative interaction of miR-203 and ZEB2 modulates tumor stemness and chemotherapy resistance in nasopharyngeal carcinoma
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Qingping Jiang1,*, Ying Zhou2,3,*, Huiling Yang2,5,*, Libo Li3,*, Xiaojie Deng2, Chao Cheng2, Yingying Xie3, Xiaojun Luo3, Weiyi Fang2,3, Zhen Liu2,4
1Department of Pathology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China
2Cancer Research Institute, Southern Medical University, Guangzhou 510515, China
3Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, Guangdong 510315, China
4Department of Pathology, Medical University of Guangzhou, Guangzhou 510182, China
5Sino-American Cancer Research Institute, Guangdong Medical College, Dongguan 523808, China
*These authors have contributed equally to this work
Weiyi Fang, email: [email protected]
Zhen Liu, email: [email protected]
Keywords: miR-203a, ZEB2, NPC, tumor stemness, chemotherapy resistance
Received: March 06, 2016 Accepted: July 18, 2016 Published: August 30, 2016
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.
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