| Autor: |
Xiao Liu, Qingdong Guo, Guangxun Gao, Zhengcong Cao, Zhihao Guan, Bo Jia, Weizhong Wang, Kuo Zhang, Wangqian Zhang, Shuning Wang, Weina Li, Qiang Hao, Yingqi Zhang, Meng Li, Wei Zhang, Jintao Gu |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Journal of Nanobiotechnology, Vol 21, Iss 1, Pp 1-25 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1477-3155 |
| DOI: |
10.1186/s12951-023-01801-w |
| Popis: |
Abstract Although temozolomide (TMZ) provides significant clinical benefit for glioblastoma (GBM), responses are limited by the emergence of acquired resistance. Here, we demonstrate that exosomal circCABIN1 secreted from TMZ-resistant cells was packaged into exosomes and then disseminated TMZ resistance of receipt cells. CircCABIN1 could be cyclized by eukaryotic translation initiation factor 4A3 (EIF4A3) and is highly expressed in GBM tissues and glioma stem cells (GSCs). CircCABIN1 is required for the self-renewal maintenance of GSCs to initiate acquired resistance. Mechanistically, circCABIN1 regulated the expression of olfactomedin-like 3 (OLFML3) by sponging miR-637. Moreover, upregulation of OLFML3 activating the ErbB signaling pathway and ultimately contributing to stemness reprogramming and TMZ resistance. Treatment of GBM orthotopic mice xenografts with engineered exosomes targeting circCABIN1 and OLFML3 provided prominent targetability and had significantly improved antitumor activity of TMZ. In summary, our work proposed a novel mechanism for drug resistance transmission in GBM and provided evidence that engineered exosomes are a promising clinical tool for cancer prevention and therapy. Graphical Abstract |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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