Exosome-mediated transfer of MIF confers temozolomide resistance by regulating TIMP3/PI3K/AKT axis in gliomas
| العنوان: | Exosome-mediated transfer of MIF confers temozolomide resistance by regulating TIMP3/PI3K/AKT axis in gliomas |
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| المؤلفون: | W.H. Tang, C.Y. Wang, Qiongzhen Huang, Q.T. Wei, X.Y. Zhong, Y.F. Lan, Jian Zhou, Changlin Lian, Y.M. Xu, Hongbo Guo, Bin Liu, H.Y. Ji |
| المصدر: | Molecular Therapy: Oncolytics, Vol 22, Iss, Pp 114-128 (2021) Molecular Therapy Oncolytics |
| بيانات النشر: | Elsevier, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Cancer Research, Temozolomide, TIMP3, Cell growth, Chemistry, Akt/PKB signaling pathway, MIF, temozolomide resistance, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, exosomes, medicine.disease, Exosome, Oncology, Glioma, glioma, medicine, Cancer research, Molecular Medicine, Pharmacology (medical), Macrophage migration inhibitory factor, Original Article, Protein kinase B, PI3K/AKT/mTOR pathway, RC254-282, medicine.drug |
| الوصف: | Temozolomide (TMZ) resistance is an important cause of clinical treatment failure and poor prognosis in gliomas. Increasing evidence indicates that cancer-derived exosomes contribute to chemoresistance; however, the specific contribution of glioma-derived exosomes remains unclear. The aim of this study was to explore the role and underlying mechanisms of exosomal macrophage migration inhibitory factor (MIF) on TMZ resistance in gliomas. We first demonstrated that MIF was upregulated in the exosomes of TMZ-resistant cells, engendering the transfer of TMZ resistance to sensitive cells. Our results indicated that exosomal MIF conferred TMZ resistance to sensitive cells through the enhancement of cell proliferation and the repression of cell apoptosis upon TMZ exposure. MIF knockdown enhanced TMZ sensitivity in resistant glioma cells by upregulating Metalloproteinase Inhibitor 3 (TIMP3) and subsequently suppressing the PI3K/AKT signaling pathway. Additionally, exosomal MIF promoted tumor growth and TMZ resistance of glioma cells in vivo, while IOS-1 (MIF inhibitor) promotes glioma TMZ sensitive in vivo. Taken together, our study demonstrated that exosome-mediated transfer of MIF enhanced TMZ resistance in glioma through downregulating TIMP3 and further activating the PI3K/AKT signaling pathway, highlighting a prognostic biomarker and promising therapeutic target for TMZ treatment in gliomas. Graphical abstract Exosomal MIF derived from TMZ-resistant cells can transfer chemoresistance character to sensitive glioma cells by downregulating TIMP3, activating the PI3K/AKT signaling pathway. ISO-1 (MIF inhibitor) is verified to be a promising treatment for TMZ resistance gliomas in animal models because it could enhance the TMZ sensitivity by inhibiting MIF. |
| اللغة: | English |
| تدمد: | 2372-7705 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::992849f17fffff774c87e30451b6c1b3 http://www.sciencedirect.com/science/article/pii/S2372770521001157 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....992849f17fffff774c87e30451b6c1b3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23727705 |
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