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N6-甲基腺苷(m6A)通过靶向上皮-间质转化和癌症干细胞作为致癌作用和耐药性的调节因子。

N6-methyladenosine (m6A) as a regulator of carcinogenesis and drug resistance by targeting epithelial-mesenchymal transition and cancer stem cells.

作者信息

Wang Chuhan, Yu Huimin, Zhuo Zhihong, Ye Zhiying

机构信息

Department of Gynecology, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, 31500, China.

Medical School of NingBo University, Ningbo, Zhejiang, 31500, China.

出版信息

Heliyon. 2023 Feb 26;9(3):e14001. doi: 10.1016/j.heliyon.2023.e14001. eCollection 2023 Mar.

Abstract

Emergence of drug resistance to chemotherapeutic agents is the principal obstacle towards curative cancer treatment in human cancer patients. It is in an urgent to explore the underlying molecular mechanisms to overcome the drug resistance. N6-Methyladenosine (m6A) RNA modification is the most abundant reversible RNA modification and has emerged in recent years to regulate gene expression in eukaryotes. Recent evidence has identified m6A is associated with cancer pathogenesis and drug resistance, contributing to the self-renewal and differentiation of cancer stem cell, tumor epithelial-mesenchymal transition (EMT) and tumor metastasis. Here we reviewed up-to-date knowledge of the relationship between m6A modulation and drug resistance. Furthermore, we illustrated the underlying mechanisms of m6A modulation in drug resistance. Lastly, we discussed the regulation of m6A modulation in EMT and cancer stem cells. Hence, it will help to provide significant therapeutic strategies to overcome drug resistance for cancer patients by changing m6A-related proteins via targeting cancer stem cells and EMT-phenotypic cells.

摘要

化疗药物耐药性的出现是人类癌症患者根治性癌症治疗的主要障碍。迫切需要探索潜在的分子机制以克服耐药性。N6-甲基腺苷(m6A)RNA修饰是最丰富的可逆RNA修饰,近年来已出现以调节真核生物中的基因表达。最近的证据表明,m6A与癌症发病机制和耐药性有关,有助于癌症干细胞的自我更新和分化、肿瘤上皮-间质转化(EMT)和肿瘤转移。在此,我们综述了m6A调控与耐药性之间关系的最新知识。此外,我们阐述了m6A调控在耐药性中的潜在机制。最后,我们讨论了m6A调控在EMT和癌症干细胞中的作用。因此,通过靶向癌症干细胞和EMT表型细胞改变m6A相关蛋白,将有助于为癌症患者提供克服耐药性的重要治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705e/10006539/3ef004c8c550/gr1.jpg

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