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长链非编码 RNA/上皮-间充质转化轴在人类癌症中的作用:肿瘤发生、化疗耐药和放疗抵抗。

Long non-coding RNA/epithelial-mesenchymal transition axis in human cancers: Tumorigenesis, chemoresistance, and radioresistance.

机构信息

Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran.

Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran; Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

出版信息

Pharmacol Res. 2022 Dec;186:106535. doi: 10.1016/j.phrs.2022.106535. Epub 2022 Nov 2.

Abstract

Epithelial-to-mesenchymal transition (EMT) is a process that involves the transformation of polarized epithelial cells to attain a mesenchymal phenotype that presents an elevated migratory potential, invasiveness, and antiapoptotic properties. Many studies have demonstrated that EMT is a prominent event that is associated with embryogenesis, tumor progression, metastasis, and therapeutic resistance. The EMT process is driven by key transcription factors (such as Snail, Twist, ZEB, and TGF-β) and several long non-coding RNAs (lncRNAs) in many non-pathological as well as pathological conditions. In the present report, we have comprehensively discussed the oncogenic and tumor suppressor role of lncRNAs and their mechanism of action in the regulation of the EMT process in various cancers such as brain tumors, gastrointestinal tumors, and gynecological and urological tumors. We have also elaborated on the role of lncRNAs in the regulation of EMT-related transcription factors (such as Snail, Twist, ZEB, and TGF-β) and therapeutic response (chemoresistance and radioresistance). Lastly, we have emphasized the role of exosomal lncRNAs in the regulation of EMT, metastasis, and therapeutic response in the aforementioned cancers. Taken together, this review provides a detailed insight into the understanding of role of lncRNAs/exosomal lncRNAs in EMT, metastasis, and therapeutic response in human cancers.

摘要

上皮-间充质转化(EMT)是一个涉及极化上皮细胞向获得更高迁移潜能、侵袭性和抗凋亡特性的间充质表型转化的过程。许多研究表明,EMT 是与胚胎发生、肿瘤进展、转移和治疗耐药相关的重要事件。EMT 过程由关键转录因子(如 Snail、Twist、ZEB 和 TGF-β)和许多非病理和病理条件下的几个长非编码 RNA(lncRNA)驱动。在本报告中,我们全面讨论了 lncRNA 的致癌和肿瘤抑制作用及其在调节各种癌症(如脑肿瘤、胃肠道肿瘤、妇科和泌尿科肿瘤)中 EMT 过程的作用机制。我们还详细阐述了 lncRNA 在调节 EMT 相关转录因子(如 Snail、Twist、ZEB 和 TGF-β)和治疗反应(化疗耐药和放射耐药)中的作用。最后,我们强调了外泌体 lncRNA 在调节上述癌症中的 EMT、转移和治疗反应中的作用。总之,本综述深入了解了 lncRNA/外泌体 lncRNA 在人类癌症中的 EMT、转移和治疗反应中的作用。

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