Over-expression of lncRNA TMEM161B-AS1 promotes the malignant biological behavior of glioma cells and the resistance to temozolomide via up-regulating the expression of multiple ferroptosis-related genes by sponging hsa-miR-27a-3p

Qiudan Chen,Yong Lin,Xiaotong Chen,Shuying Chen,Yuan Lv,Zhong Wu,Weifeng Wang,Shihao Zhuang,Guanglei Song

doi:10.1038/s41420-021-00709-4

Abstract

A growing body of evidence suggests that long-chain non-coding RNA (lncRNA) plays an important role in the malignant biological behavior and drug resistance of glioblastoma (GBM) cells. In this study, we analyzed the role and potential mechanism of lncRNA TMEM161B-AS1 in the malignant biological behavior of GBM cells and temozolomide (TMZ) resistance. Studies have found that FANCD2 and CD44 are significantly related to the occurrence of GBM, TMZ resistance and the survival of GBM patients. Knockdown of TMEM161B-AS1 down-regulated the expression of FANCD2 and CD44 by sponging hsa-miR-27a-3p, inhibited the proliferation, migration, invasion and promoted apoptosis, ferroptosis of U87 cells and U251 cells. Down-regulation of lncRNA TMEM161B-AS1 and/or over-expression of hsa-miR-27a-3p down-regulated the expression of FANCD2 and CD44, and inhibited the tumor growth in nude mice. These results demonstrated that the lncRNA TMEM161B-AS1-hsa-miR-27a-3p-FANCD2/CD44 signal axis regulated the malignant biological behavior of GBM and TMZ resistance. These findings were expected to provide promising therapeutic targets for the treatment of glioma.

Highlights

Glioblastoma (GBM) is a primary central nervous system tumor with the highest incidence, high malignancy, and poor prognosis in adults [1,2,3]
This study aimed to study the possible function of long-chain non-coding RNA (lncRNA) TMEM161B-AS1- hsa-miR-27a-3p- Fanconi anemia complementation group D2 (FANCD2)/CD44 crosstalk in the malignant biological behavior of GBM and TMZ resistance
We found that 11 genes were both up-regulated in glioma cells and TMZ-insensitive U251 cells, namely ZIC1, TMEM154, PRRX1, ITGA4, APOBEC3F, ADAM12, ANTXR2, PHLDA1, CALCRL, GALNT5 and CD44 (Fig. 1c)

Summary

Introduction

Glioblastoma (GBM) is a primary central nervous system tumor with the highest incidence, high malignancy, and poor prognosis in adults [1,2,3]. Standard treatment of GBM is neurosurgical resection, combined with radiotherapy and chemotherapy [4,5,6,7,8]. Due to the diffuse invasive growth characteristics of GBM, the tumors cannot be completely removed by surgical means [9]. GBM stem cells (GSC) in GBM give tumors the characteristics of genetic heterogeneity and abnormal microvascular proliferation, making them resistant to radiotherapy and chemotherapy [10,11,12]. The clinical application of TMZ has been hampered by resistance of GBM cells [15, 16]. It is important to elucidate mechanisms of TMZ resistance in GBM

Objectives

Methods

Results

Conclusion