miR-876-5p exerts tumor suppressor function by targeting TWIST1 and regulating the epithelial-mesenchymal transition in glioblastoma

Objective: Glioblastoma (GBM) remains one of the most lethal types of cancer, and is the most common brain tumor in adults. The purpose of this study was to determine the role of miR-876-5p in regulation of epithelial mesenchymal transition (EMT) and metastasis of GBM cells. Materials and methods: TWIST1 and miR-876-5p expression was analyzed by real-time PCR and Western blot assays. We confirmed the association between miR-876-5p and TWIST1 by dual luciferase reporter assay. The roles of the miR-876-5p/TWIST1 pathway in migration and invasion were examined in vitro. The effects of miR-876-5p on EMT-related molecules E-cadherin, N-cadherin and vimentin were evaluated by real-time PCR and Western blot. Results: miR-876-5p expression levels were decreased while TWIST1 expression levels were increased in detected GBM tissue samples and all of the GBM cell lines. In addition, ectopic expression of miR-876-5p suppressed and miR-876-5p-in promoted EMT, migration, and invasion in T98G cells. Bioinformatics coupled with luciferase and Western blot assays also revealed that miR-876-5p inhibited expression of TWIST1, one of the master regulators of tumor metastasis. Conclusions: This study first indicates that miR-876-5p functions as a suppressor in regulating of GBM EMT by targeting TWSIT1, and it promise as a therapeutic target and prognostic marker for metastatic GBM.