Overexpression of microRNA-129-5p in glioblastoma inhibits cell proliferation, migration, and colony-forming ability by targeting ZFP36L1.

Xu Guo,Ye Zhang,Bing Yao,Haozhe Piao,Peixin Sun

doi:10.17305/bjbms.2019.4503

Abstract

Glioblastoma multiforme (GBM) is a highly invasive cancer with a high recurrence rate. The prognosis of GBM patients remains poor, even after standard surgical resection combined with chemoradiotherapy. Thus, there is an urgent need for new therapeutic targets in GBM. In recent years, microRNAs have received considerable attention due to their important role in tumor development and progression. In this study, we investigated the role of miR-129-5p and miR-129-5p/ZFP36L1 axis in GBM tumorigenesis. Analysis of GSE103228 microarray data from the GEO database showed that miR-129-5p was significantly downregulated in GBM vs. normal brain tissues. Quantitative reverse transcription PCR analysis of miR-129-5p expression in seven GBM cell lines (LN229, A172, U87, T98G, U251, H4, and LN118) vs. normal human astrocytes (NHA) showed miR-129-5p was significantly downregulated in GBM cells. Overexpression of miR-129-5p in LN229 and A172 cells significantly suppressed cell proliferation, migration, invasion, and colony-forming ability. Target Scan analysis identified ZFP36L1 as the target of miR-129-5p. UALCAN dataset analysis found that ZFP36L1 was significantly upregulated in GBM vs. normal brain tissues, and high ZFP36L1 expression was positively associated with poor survival of GBM patients. Western blot analysis demonstrated that ZFP36L1 was significantly upregulated in seven GBM cell lines vs. NHA. Overexpression of miR-129-5p in LN229 and A172 cells significantly inhibited ZFP36L1 mRNA and protein expression, while overexpression of ZFP36L1 in LN229 and A172 cells reversed miR-129-5p-mediated inhibition on GBM tumorigenesis. Our results revealed an important role of miR-129-5p in the negative regulation of ZFP36L1 expression in GBM, suggesting new candidates for targeted therapy in GBM patients.

Highlights

Glioma accounts for the largest category of primary brain tumors among which glioblastoma multiforme (GBM) is the most aggressive brain tumor
After analyzing 3557 differentially expressed microRNAs, we found that the expression of miR-129-5p was significantly downregulated in GBM tissues vs. normal brain tissues (p < 0.005, Figure 1A)
We demonstrated that miR-129-5p and miR129-5p-regulated target gene ZFP36 ring finger protein-like 1 (ZFP36L1) are involved in GBM

Summary

Introduction

Glioma accounts for the largest category of primary brain tumors among which glioblastoma multiforme (GBM) is the most aggressive brain tumor. GBM accounts for about 14.7% of all primary and metastatic tumors of the brain [1]. The incidence of GBM has been increasing year by year, while the incidence of other glioma types has been gradually decreasing [2]. In the USA and Europe, the incidence of GBM is 2 to 3 per 100,000 people [3]. GBM is the most malignant type of astrocytoma, and the clinical manifestations are headache, convulsions, and psychiatric symptoms. Other typical features of Department of Neurosurgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China

Methods

Results

Conclusion