MiRNA-27a-3p induces temozolomide resistance in glioma by inhibiting NF1 level

Shenglan Li; Wei Li; Gang Chen; Jing Huang; Wenbin Li

MiRNA-27a-3p induces temozolomide resistance in glioma by inhibiting NF1 level

Am J Transl Res. 2020 Aug 15;12(8):4749-4756. eCollection 2020.

Authors

Shenglan Li¹, Wei Li², Gang Chen³, Jing Huang⁴, Wenbin Li¹

Affiliations

¹ Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University Beijing, China.
² Department of Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University Beijing, China.
³ Beijing Qinglian Biotech Co., Ltd. Beijing, China.
⁴ Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University Beijing, China.

PMID: 32913547
PMCID: PMC7476123

Abstract

To elucidate the role of miRNA-27a-3p in inducing Temozolomide (TMZ) resistance in glioma and the underlying mechanism. Relative levels of miRNA-27a-3p and NF1 in glioma tissues and peritumoral ones were detected. In addition, their levels in TMZ-sensitive and TMZ-resistant glioma tissues were examined as well. TMZ-resistant glioma cell lines SHG44-TG and U87-TR were used for in vitro experiments. Relative levels of miRNA-27a-3p and NF1 in TMZ-resistant glioma cells and their parental cells were determined. Subsequently, regulatory effects of miRNA-27a-3p on IC₅₀ value of TMZ, viability and migratory ability in SHG44-TG and U87-TR cells were assessed. The interaction between miRNA-27a-3p and NF1 was evaluated by luciferase assay and Western blot. MiRNA-27a-3p was upregulated in glioma tissues than controls, especially TMZ-resistant ones, whereas NF-1 displayed a negative correlation to miRNA-27a-3p as its downstream target. Overexpression of miRNA-27a-3p increased IC₅₀ value of TMZ, viability and migratory ability in SHG44-TG and U87-TR cells. Regulatory effects of miRNA-27a-3p on phenotypes of TMZ-resistant glioma cells were abolished by overexpression of NF1. MiRNA-27a-3p induces TMZ resistance in glioma by negatively regulating NF1 level.

Keywords: MiRNA-27a-3p; NF1; drug resistance; glioma; temozolomide.