Knockdown of NEAT1 restrained the malignant progression of glioma stem cells by activating microRNA let-7e.

Wei Gong,Xiaobai Liu,Yixue Xue,Jun Ma,Jian Zheng,Yunhui Liu

doi:10.18632/oncotarget.11403

Abstract

Nuclear paraspeckle assembly transcript 1 (NEAT1), a long non-coding RNA, promotes oncogenesis in various tumors, including human gliomas. Herein, we studied the expression and function of NEAT1 in glioma stem cells (GSCs). Quantitative real-time PCR demonstrated that NEAT1 was upregulated in GSCs. NEAT1 knockdown inhibited GSC cell proliferation, migration and invasion and promoted GSC apoptosis. A potential binding region between NEAT1 and microRNA let-7e was confirmed by dual-luciferase assays. Upregulation of NEAT1 reduced the expression of let-7e, and there was reciprocal repression between NEAT1 and let-7e in an Argonaute 2-dependent manner. Let-7e expression was lower expression in glioblastoma tissues and GSCs than in normal brain tissues and cells. Restoration of let-7e suppressed tumor function by inhibiting proliferation, migration and invasion while promoting apoptosis in GSCs. NEAT1 knockdown and let-7e overexpression both reduced NRAS protein expression. NRAS was identified as a direct target of let-7e and promoted oncogenesis in GSCs. As NEAT1 promoted oncogenesis by downregulating let-7e expression, both of these genes could be considered for application in glioma therapy.

Highlights

Glioma is one of the most prevalent and aggressive primary brain tumors in adults
NRAS was identified as a direct target of let-7e and promoted oncogenesis in glioma stem cells (GSCs)
We demonstrated that Nuclear paraspeckle assembly transcript 1 (NEAT1) was upregulated in GSCs

Summary

Introduction

Glioma is one of the most prevalent and aggressive primary brain tumors in adults. Despite treatment with advanced therapeutic strategies, patients with this disease only have a median survival of 15 months [1]. GSCs are important contributors to the malignant progression of glioma, from its development to therapeutic resistance and recurrence [3]. It is urgent to discover the molecular mechanisms by which GSCs are maintained, as this would provide a new focus for the development of glioma treatments. LncRNAs are ubiquitously dysregulated in tumor cells and have crucial regulatory roles in the malignant progression of tumor cells, such as promotes or suppresses proliferation, migration and invasion, and apoptosis [6]. NEAT1 is upregulated and has important functions in a variety of cancers including glioma, such as favors cell proliferation, migration and invasion and impaired apoptosis [10,11,12,13]. Whether NEAT1 is associated with the malignant progression of GSCs remains unclear

Methods

Results

Conclusion