Oncogenic ZEB2/miR-637/HMGA1 signaling axis targeting vimentin promotes the malignant phenotype of glioma

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Yu ZengYe Song

Abstract

Background Glioma is the most common primary tumor of the central nervous system. We previously confirmed that zinc finger E-box binding homeobox (ZEB) 2 promotes the malignant progression of glioma, while microRNA-637 (miR-637) is associated with favorable prognosis in glioma. This study investigated the potential interaction between ZEB2 and miR-637 and its downstream signaling pathway in glioma. Methods Chromatin immunoprecipitation, luciferase reporter, and electrophoretic mobility shift assays were used to confirm ZEB2 binding to miR-637. Microarray and bioinformatic analyses were used to investigate targets of miR-637. MTT and EdU assays, transwell assays, and Boyden assays were utilized to assess cell viability, migration, and invasion, respectively. A subcutaneous xenograft model was utilized for analyzing the role of miR-637/high mobility group A1 (HMGA1) interaction in vivo. Immunohistochemistry staining of clinical samples and bioinformatic analysis of the Chinese Glioma Genome Atlas and The Cancer Genome Atlas databases were performed to further confirm the ZEB2/miR-637/HMGA1/vimentin axis. Results ZEB2 was bound directly bind to the E-box elements in the miR-637 promoter and promoted cell proliferation, migration, ...Continue Reading

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