CRISPR-mediated MECOM Depletion Retards Tumor Growth by Reducing Cancer Stem Cell Properties in Lung Squamous Cell Carcinoma

Overview

Journal Mol Ther

Publisher Cell Press

Specialties Molecular Biology
Pharmacology

Date 2022 Jun 23

PMID 35733338

Authors

Yuanyuan Ma

Bin Kang

Shaolei Li

Guoyun Xie

Jiwang Bi

Fuqiang Li

Guo An

Bing Liu

Jing Li

Yue Shen

Xun Xu

Huanming Yang

Yue Yang

Ying Gu

Nan Wu

Affiliations

Soon will be listed here.

Abstract

Targeted therapy for lung squamous cell carcinoma (LUSC) remains a challenge due to the lack of robust targets. Here, we identified MECOM as a candidate of therapeutic target for LUSC by screening 38 genes that were commonly amplified in three pairs of primary tumors and patient-derived xenografts (PDXs) using a clustered regularly interspaced short palindromic repeats (CRISPR)-mediated approach. High MECOM expression levels were associated with poor prognosis. Forced expression of MECOM in LUSC cell lines promoted cancer stem cell (CSC) properties, and its knockout inhibited CSC phenotypes. Furthermore, systemic delivery of CRISPR-mediated MECOM depletion cassette using adenovirus with an adaptor, which is composed of a single-chain fragment variable (scFv) against epithelial cell adhesion molecules (EpCAM) fused to the ectodomain of coxsackievirus and adenovirus receptor, and a protector, which consists of the scFv connected to the hexon symmetry of the adenovirus, could specifically target subcutaneous and orthotopic LUSC and retard tumor growth. This study could provide a novel therapeutic strategy for LUSC with high efficacy and specificity.

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