To Kenneth K W, Zhang Hang, Cho William C
School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China.
Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong SAR 999077, China.
Cancer Drug Resist. 2024 Sep 25;7:37. doi: 10.20517/cdr.2024.66. eCollection 2024.
Competing endogenous RNAs (ceRNAs) are transcripts that possess highly similar microRNA response elements (MREs). microRNAs (miRNAs) are short, endogenous, single-stranded non-coding RNAs (ncRNAs) that can repress gene expression by binding to MREs on the 3' untranslated regions (UTRs) of the target mRNA transcripts to suppress gene expression by promoting mRNA degradation and/or inhibiting protein translation. mRNA transcripts, circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and transcribed pseudogenes could share similar MREs, and they can compete for the same pool of miRNAs. These ceRNAs may affect the level of one another by competing for their shared miRNAs. This interplay between different RNAs constitutes a ceRNA network, which regulates many important biological processes. Cancer drug resistance is a major factor leading to treatment failure in patients receiving chemotherapy. It can be acquired through genetic, epigenetic, and various tumor microenvironment mechanisms. The involvement of ceRNA crosstalk and its disruption in chemotherapy resistance is attracting attention in the cancer research community. This review presents an updated summary of the latest research on ceRNA dysregulation causing drug resistance across different cancer types and chemotherapeutic drug classes. Interestingly, accumulating evidence suggests that ceRNAs may be used as prognostic biomarkers to predict clinical response to cancer chemotherapy. Nevertheless, detailed experimental investigations of the putative ceRNA networks generated by computational algorithms are needed to support their translation for therapeutic and prognostic applications.
竞争性内源RNA（ceRNA）是具有高度相似微小RNA反应元件（MRE）的转录本。微小RNA（miRNA）是短的、内源性的、单链非编码RNA（ncRNA），它可以通过与靶mRNA转录本3'非翻译区（UTR）上的MRE结合来抑制基因表达，通过促进mRNA降解和/或抑制蛋白质翻译来实现。mRNA转录本、环状RNA（circRNA）、长链非编码RNA（lncRNA）和转录假基因可能共享相似的MRE，并且它们可以竞争同一组miRNA。这些ceRNA可能通过竞争其共享的miRNA来相互影响水平。不同RNA之间的这种相互作用构成了一个ceRNA网络，该网络调节许多重要的生物学过程。癌症耐药性是导致接受化疗的患者治疗失败的主要因素。它可以通过遗传、表观遗传和各种肿瘤微环境机制获得。ceRNA串扰及其在化疗耐药性中的破坏作用在癌症研究领域正受到关注。本综述对不同癌症类型和化疗药物类别中导致耐药性的ceRNA失调的最新研究进行了更新总结。有趣的是，越来越多的证据表明ceRNA可能用作预测癌症化疗临床反应的预后生物标志物。然而，需要对由计算算法生成的假定ceRNA网络进行详细的实验研究，以支持它们在治疗和预后应用中的转化。
