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01-07-2018 | Laboratory Investigation

miR-1268a regulates ABCC1 expression to mediate temozolomide resistance in glioblastoma

Authors: Yaomin Li, Yawei Liu, Jing Ren, Shengze Deng, Guozhong Yi, Manlan Guo, Songren Shu, Liang Zhao, Yuping Peng, Songtao Qi

Published in: Journal of Neuro-Oncology | Issue 3/2018

Abstract

Introduction

Temozolomide (TMZ) is the preferred chemotherapeutic drug approved for the Glioblastoma multiforme (GBM) treatment. However, resistance to TMZ is the most intractable challenge for treatment of GBM. Screening of miRNAs is becoming a novel strategy to reveal underlying mechanism of drug-resistance of human tumors.

Materials and methods

We conducted RNA sequencing (RNA-seq) for GBM cells treated continuously with TMZ 1 or 2 week or not. Bioinformatic analysis was used to predict targets of these altered miRNAs. Subsequently, we studied the potential role of miR-1268a in TMZ-resistance of GBM cells.

Results

Expression levels of 55 miRNAs were identified altering both after 1 and 2 weeks TMZ treatment. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to illuminate the biological implication and related pathways of predicted target genes. We showed that miR-1268a was downregulated after TMZ treatment and targeted ABCC1/MRP1, a membrane transporter contributing to drug resistance, using dual-luciferase assay. Furthermore, we confirmed overexpression of miR-1268a inhibited protein translation of ABCC1 and restored upregulated expression of ABCC1 due to TMZ. Inversely, knockdown of miR-1268a increased ABCC1 at protein level and enhanced upregulation of ABCC1 with TMZ treatment. In addition, our data indicated that miR-1268a enhanced TMZ sensitivity in GBM cells.

Conclusion

Through RNA-seq analysis, we discovered miR-1268a and elucidated its role in modulating TMZ-resistance of GBM cells by targeting ABCC1.

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Title: miR-1268a regulates ABCC1 expression to mediate temozolomide resistance in glioblastoma
Authors: Yaomin Li
Yawei Liu
Jing Ren
Shengze Deng
Guozhong Yi
Manlan Guo
Songren Shu
Liang Zhao
Yuping Peng
Songtao Qi
Publication date: 01-07-2018
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 3/2018
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-018-2835-3

At a glance: The STEP trials

Springer Medicine

miR-1268a regulates ABCC1 expression to mediate temozolomide resistance in glioblastoma

Abstract

Introduction

Materials and methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Introduction

Materials and methods

Results

Conclusion

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