CRISPR-Cas Knockout of MiR21 Reduces Glioma Growth

Overview

Journal Mol Ther Oncolytics

Publisher Cell Press

Date 2022 May 16

PMID 35572197

Authors

Lisa Nieland

Thomas S van Solinge

Pike See Cheah

Liza M Morsett

Joseph El Khoury

Joseph I Rissman

Benjamin P Kleinstiver

Marike L D Broekman

Xandra O Breakefield

Erik R Abels

Affiliations

Soon will be listed here.

Abstract

Non-coding RNAs, including microRNAs (miRNAs), support the progression of glioma. miR-21 is a small, non-coding transcript involved in regulating gene expression in multiple cellular pathways, including the regulation of proliferation. High expression of miR-21 has been shown to be a major driver of glioma growth. Manipulating the expression of miRNAs is a novel strategy in the development of therapeutics in cancer. In this study we aimed to target miR-21. Using CRISPR genome-editing technology, we disrupted the miR-21 coding sequences in glioma cells. Depletion of this miRNA resulted in the upregulation of many downstream miR-21 target mRNAs involved in proliferation. Phenotypically, CRISPR-edited glioma cells showed reduced migration, invasion, and proliferation . In immunocompetent mouse models, miR-21 knockout tumors showed reduced growth resulting in an increased overall survival. In summary, we show that by knocking out a key miRNA in glioma, these cells have decreased proliferation capacity both and . Overall, we identified miR-21 as a potential target for CRISPR-based therapeutics in glioma.

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