Hypoxia-Induced MiR-137 Inhibition Increased Glioblastoma Multiforme Growth and Chemoresistance Through LRP6

Overview

Journal Front Oncol

Specialty Oncology

Date 2021 Mar 15

PMID 33718112

Citations 13

Authors

Dong-Mei Li

Qiu-Dan Chen

Gui-Ning Wei

Jie Wei

Jian-Xing Yin

Jun-Hui He

Xin Ge

Zhu-Mei Shi

Affiliations

Soon will be listed here.

Abstract

Purpose: Glioblastoma multiforme (GBM) is one of the deadliest tumors, which is involved in numerous dysregulated microRNAs including miR-137. However, the mechanism of how miR-137 suppression associated with cancer progression and chemoresistance still remains to be elucidated.

Methods: Quantitative reverse transcriptase-PCR (qRT-PCR), DNA methylation analysis, cell proliferation assay, flow cytometric analysis, invasion assay, tumor formation experiment were performed to test the expression levels and functions of miR-137 in GBM. Bioinformatics analysis, luciferase reporter assay, qRT-PCR, immunoblotting, immunofluorescence, and immunohistochemistry assay were used to identify and verify the target of miR-137.

Results: We found that miR-137 was downregulated in primary and recurrent GBM compared with normal brain tissues. Overexpression of miR-137 inhibited cell invasion and enhanced cell chemosensitivity to temozolomide (TMZ) by directly targeting low-density lipoprotein receptor-related protein 6 (LRP6) in GBM. Forced expression of LRP6 cDNA without its 3'-UTR region partly restored the effects of miR-137 and . Hypoxia-induced miR-137 methylation was responsible for the miR-137 suppression, leading to the cell chemoresistance and poor prognosis of GBM.

Conclusions: These findings demonstrated the detailed molecular mechanism of miR-137 in regulating GBM growth and chemoresistance in hypoxia microenvironment, suggesting the potentiality of miR-137 as a therapeutic target for GBM.

Citing Articles

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The multifaceted therapeutical role of low-density lipoprotein receptor family in high-grade glioma.

Mastrantuono E, Ghibaudi M, Matias D, Battaglia G Mol Oncol. 2024; 18(12):2966-2976.

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Palizkaran Yazdi M, Barjasteh A, Moghbeli M Mol Brain. 2024; 17(1):42.

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Elgebaly S, Peacock W, Christenson R, Kreutzer D, Hassan Ibrahim Faraag A, Sarguos A Int J Mol Sci. 2023; 24(19).

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Alcaniz J, Winkler L, Dahlmann M, Becker M, Orthmann A, Haybaeck J Front Oncol. 2023; 13:1129627.

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