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EMT 相关 lncRNAs 在治疗抵抗中的新作用及其作为生物标志物的应用。

The Emerging Role of EMT-related lncRNAs in Therapy Resistance and their Applications as Biomarkers.

机构信息

Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.

Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians University Munich, Munich, Germany.

出版信息

Curr Med Chem. 2022;29(26):4574-4601. doi: 10.2174/0929867329666220329203032.

Abstract

Cancer is the world's second-largest cause of death. The most common cancer treatments are surgery, radiation therapy, and chemotherapy. Drug resistance, epithelial-- to-mesenchymal transition (EMT), and metastasis are pressing issues in cancer therapy today. Increasing evidence showed that drug resistance and EMT are co-related with each other. Indeed, drug-resistant cancer cells possess enhanced EMT and invasive ability. Recent research has demonstrated that lncRNAs (long non-coding RNAs) are non-coding transcripts which play an important role in the regulation of EMT, metastasis, and drug resistance in different cancers. However, the relationships among lncRNAs, EMT, and drug resistance are still unclear. These effects could be exerted via several signaling pathways, such as TGF-β, PI3K-AKT, and Wnt/β-catenin. Identifying the crucial regulatory roles of lncRNAs in these pathways and processes leads to the development of novel targeted therapies. We review the key aspects of lncRNAs associated with EMT and therapy resistance. We focus on the crosstalk between lncRNAs and molecular signaling pathways affecting EMT and drug resistance. Moreover, each of the mentioned lncRNAs could be used as a potential diagnostic, prognostic, and therapeutic therapy resistancefor cancer. However, the investigation of lncRNAs for clinical applications still has several challenges.

摘要

癌症是全球第二大死亡原因。最常见的癌症治疗方法是手术、放射疗法和化学疗法。耐药性、上皮-间质转化 (EMT) 和转移是当今癌症治疗中的紧迫问题。越来越多的证据表明,耐药性和 EMT 相互关联。事实上,耐药性癌细胞具有增强的 EMT 和侵袭能力。最近的研究表明,lncRNAs(长非编码 RNA)是一类非编码转录本,在不同癌症的 EMT、转移和耐药性调控中发挥重要作用。然而,lncRNAs、EMT 和耐药性之间的关系尚不清楚。这些作用可能通过几种信号通路发挥,如 TGF-β、PI3K-AKT 和 Wnt/β-catenin。确定 lncRNAs 在这些通路和过程中的关键调控作用,可导致新型靶向治疗的发展。我们综述了与 EMT 和治疗耐药性相关的 lncRNAs 的关键方面。我们重点关注 lncRNAs 与影响 EMT 和耐药性的分子信号通路之间的相互作用。此外,提到的每一个 lncRNA 都可以作为癌症潜在的诊断、预后和治疗耐药性的标志物。然而,lncRNAs 的临床应用研究仍面临一些挑战。

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