The role of microRNA-148a and downstream DLGAP1 on the molecular regulation and tumor progression on human glioblastoma

Yue Li,Xuemei Tang,Feiya Zhong,Thomas J Rosol,Xiaoning Peng,Shan Zhang,Xiyun Deng,Xiangni Peng,Xiaomin Zeng,Zhonghua Liu,Weiguo Li,Sihua Peng,Yang Zhong

doi:10.1038/s41388-019-0922-3

Abstract

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Currently, the prognosis of the patients with GBM is very poor and new molecular targets and treatment strategies are urgently needed to combat it. MicroRNA-148a (miR-148a) has been shown to be dysregulated in certain tumor types. However, the role of miR-148a in the pathogenesis of GBM is not fully understood. Here we comprehensively analyzed the roles of miR-148a, downstream DLGAP1, and their molecular pathways in GBM. We showed that miR-148a promote the proliferation and growth of GBM cells both in vitro and in vivo, and also induced the migration, invasion, and EMT (epithelial–mesenchymal transition) program of GBM cells by directly targeting DLGAP1. Furthermore, we identified 31 new miR-148a targets and found that miR-148a function was mainly involved in the cell adhesion signaling pathway and was associated with nervous system diseases. Our findings provide a new mechanism for miR-148a-mediated GBM cell invasion and reveal previously unreported targets of miR-148a as well as novel miR-148a-mediated regulatory networks in GBM. These results increase the understanding of the role of miR-148a in GBM and may lead to novel therapeutic strategies for GBM.

Highlights

Glioma is the most common intracranial tumor, accounting for 70% of brain tumors [1]
We demonstrated that miR-148a was upregulated, DLGAP1 was downregulated in GBM, and DLGAP1 was a direct target of miR-148a. miR-148a promoted the proliferation and survival of GBM cells, and miR-148a promoted the migration, invasion, and EMT of GBM cells, which was mediated by DLGAP1
We further analyzed the relationship between miR-148a and miR-148a promoted the proliferation of GBM cells and enhanced tumor growth

Summary

Introduction

Glioma is the most common intracranial tumor, accounting for 70% of brain tumors [1]. It was found that the expression of miR-148a was upregulated in GBM and the high expression of miR-148a promoted the proliferation, migration, and invasion, and inhibited the apoptosis of GBM cells [5, 12, 13]. These findings indicate that miR-148a may have tissue-specific biological effects. The role of miR-148a on the migration and invasion of GBM cells by regulating DLGAP1 is worthy of investigation. The results of this study discovered new targets of miR-148a and their molecular regulatory networks, which provided critical insight into the role of miR-148a in GBM

Results

Materials and methods

Compliance with ethical standards