miR-29b and miR-125a regulate podoplanin and suppress invasion in glioblastoma

miR-29b 和 miR-125a 调节平足蛋白并抑制胶质母细胞瘤的侵袭

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作者:Maria Angelica Cortez, Milena Sabrina Nicoloso, Masayoshi Shimizu, Simona Rossi, Gopal Gopisetty, Jennifer R Molina, Carlos Carlotti Jr, Daniela Tirapelli, Luciano Neder, Maria Sol Brassesco, Carlos Alberto Scrideli, Luiz Gonzaga Tone, Maria-Magdalena Georgescu, Wei Zhang, Vinay Puduvalli, George Ad

Abstract

Glioblastoma is the most frequent and malignant brain tumor, characterized by an elevated capacity for cellular proliferation and invasion. Recently, it was demonstrated that podoplanin membrane sialo-glycoprotein encoded by PDPN gene is over-expressed and related to cellular invasion in astrocytic tumors; however the mechanisms of regulation are still unknown. MicroRNAs are noncoding RNAs that regulate gene expression and several biological processes and diseases, including cancer. Nevertheless, their roles in invasion, proliferation, and apoptosis of glioblastoma are not completely understood. In this study, we focused on miR-29b and miR-125a, which were predicted to regulate PDPN, and demonstrated that these microRNAs directly target the 3' untranslated region of PDPN and inhibit invasion, apoptosis, and proliferation of glioblastomas. Furthermore, we report that miR-29b and miR-125a are downregulated in glioblastomas and also in CD133-positive cells. Taken together, these results suggest that miR-29b and miR-125a represent potential therapeutic targets in glioblastoma.

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