Overexpression of miR-29a reduces the oncogenic properties of glioblastoma stem cells by downregulating Quaking gene isoform 6.

Ping Wang,Xiaobai Liu,Zhiqing Li,Min Bao,Zhen Li,Chao Shang,Jun Ma,Zhuo Xi,Yixue Xue,Yunhui Liu

doi:10.18632/oncotarget.15327

Abstract

Glioblastoma is the most common type of malignant primary brain tumor and has high recurrence and lethality rates. Glioblastoma stem cells (GSCs), a subpopulation of glioblastoma cells, may promote rapid tumor recurrence and therapy resistance. Because altered microRNA (miR) expression in GSCs may lead to glioblastoma progression, we assessed the effects of miR-29a expression on the oncogenic behavior of GSCs. MiR-29a expression was lower in GSCs than non-GSCs, and overexpression of miR-29a in GSCs inhibited cell proliferation, migration and invasion, but promoted apoptosis. MiR-29a directly inhibited the expression of Quaking gene isoform 6 (QKI-6) by binding to its 3′-UTR, and thus inhibited GSC malignant behavior. In addition, Wilms’ tumor 1-associating protein (WTAP) was identified as a downstream target of QKI-6. Overexpression of miR-29a in GSCs inhibited expression of WTAP and suppressed both phosphoinositide 3-kinase/AKT and extracellular signal-related kinase pathways by downregulating QKI-6, thereby inhibiting cell proliferation, migration, and invasion but promoting apoptosis. We have characterized a novel miR-29a/QKI-6/WTAP axis in GSCs, which may provide theoretical support for the treatment of glioblastoma with miR-29a agomirs.

Highlights

Glioblastoma, regarded as a grade IV astrocytoma, is the most common and malignant type of primary brain tumor
In Glioblastoma stem cells (GSCs)-U251 and GSCs-GTD, the apoptosis rates were significantly increased by 7.1% (P
Xu et al reported that downregulation of miR-29a suppressed the malignant behavior of the U87 cell line [19]; the expression and function of miR-29a in GSCs has remained unclear

Summary

Introduction

Glioblastoma, regarded as a grade IV astrocytoma, is the most common and malignant type of primary brain tumor. Some studies have demonstrated that glioblastomas contain a small subpopulation of cells with the ability to self-renew and to initiate brain tumors. These cells are considered to be glioblastoma stem cells (GSCs), which promote tumor progression, treatment resistance, and tumor recurrence [1,2,3]. Many recent studies have revealed that miRNAs regulate the behavior of GSCs and may have similar functions to oncogenes or tumor suppressors [4]. While miR-29a expression has been reported to be reduced in gliomas [9], the molecular pathways regulated by miR-29a and their influence on GSC biological processes are not yet known

Methods

Results

Conclusion