OncoTargets and Therapy (Nov 2019)
MicroRNA-188-5p Promotes Epithelial–Mesenchymal Transition by Targeting ID4 Through Wnt/β-catenin Signaling in Retinoblastoma
Abstract
Ming Yang, Yang Li, Wenbin Wei Beijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, People’s Republic of ChinaCorrespondence: Wenbin WeiBeijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing Tongren Hospital, Capital Medical University, No. 1 DongJiaoMinXiang, Dongcheng District, Beijing 100730, People’s Republic of ChinaTel +86-13701255115Email [email protected]: Here, we investigated the involvement of the miR-188-5p/inhibitor of the DNA binding 4 (ID4) axis in retinoblastoma (Rb).Patients and methods: We included 35 Rb tissues and the corresponding adjacent normal tissues. RT-qPCR, Western blot, lentivirus transfection, measurement of cell migration in vitro, and chip analysis were performed during the study. Mouse Rb models were established to investigate the in vivo mechanisms.Results: We showed that miR-188-5p was upregulated in Rb tissues; moreover, we identified a pathway involving the upregulation of miR-188-5p and its downstream target, ID4, in vitro. Cell experiments revealed that the overexpression of miR-188-5p significantly downregulated the expression of ID4 and the underlying mechanism involved direct targeting of the ID4 3′-UTR. The levels of ID4 are lower in Rb tissues; it plays an antitumor role by inhibiting Rb metastasis in vitro and in vivo. Further investigation revealed that the miR-188-5p/ID4 axis regulated metastasis by promoting epithelial–mesenchymal transition (EMT). We demonstrated that microRNA-188-5p promoted EMT by targeting ID4 through Wnt/β catenin signaling in Rb.Conclusion: miRNA-188-5p can promote EMT by targeting ID4 through the Wnt/β‑catenin signaling pathway.Keywords: retinoblastoma, miRNA-188-5p, ID4, epithelial-mesenchymal transition, Wnt/β catenin signaling
