CRISPR-Cas9 library screening combined with an exosome-targeted delivery system addresses tumorigenesis/TMZ resistance in the mesenchymal subtype of glioblastoma

作者：Jixing Zhao, Xiaoteng Cui, Zhan Qi, Kailiang Zhang, Dongyuan Su, Shixue Yang, Biao Hong, Qixue Wang, Jiasheng Ju, Chunchao Cheng, Chen Li, Chunxiao Wan, Yunfei Wang, Junhu Zhou, Chunsheng Kang · 发表于：Theranostics · 年份：2024 · DOI：10.7150/thno.92703 · 被引用次数：42 · 研究领域：Extracellular vesicles in disease、MicroRNA in disease regulation、interferon and immune responses

We demonstrate a new mechanism by which ERBIN is epigenetically silenced by the RAS signaling in the MES subtype of GBM. Restoration of the ERBIN expression with EPIC-0412 significantly inhibits the RAS signaling downstream. RASGRP1 and VPS28 genes are associated with the promotion of TMZ resistance through RAS-GDP to RAS-GTP transformation and TMZ efflux, as well. A quadruple combination therapy based on a targeted Exos delivery system demonstrated significantly reduced tumor burden in vivo. Therefore, our study provides new insights and therapeutic approaches for regulating tumor progression and TMZ resistance in the MES-GBM subtype.