Utilizing non-coding RNA-mediated regulation of ATP binding cassette (ABC) transporters to overcome multidrug resistance to cancer chemotherapy

IF 15.8 1区 医学 Q1 PHARMACOLOGY & PHARMACY
Kenneth K.W. To , Zoufang Huang , Hang Zhang , Charles R. Ashby Jr. , Liwu Fu
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Abstract

Multidrug resistance (MDR) is one of the primary factors that produces treatment failure in patients receiving cancer chemotherapy. MDR is a complex multifactorial phenomenon, characterized by a decrease or abrogation of the efficacy of a wide spectrum of anticancer drugs that are structurally and mechanistically distinct. The overexpression of the ATP-binding cassette (ABC) transporters, notably ABCG2 and ABCB1, are one of the primary mediators of MDR in cancer cells, which promotes the efflux of certain chemotherapeutic drugs from cancer cells, thereby decreasing or abolishing their therapeutic efficacy. A number of studies have suggested that non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), play a pivotal role in mediating the upregulation of ABC transporters in certain MDR cancer cells. This review will provide updated information about the induction of ABC transporters due to the aberrant regulation of ncRNAs in cancer cells. We will also discuss the measurement and biological profile of circulating ncRNAs in various body fluids as potential biomarkers for predicting the response of cancer patients to chemotherapy. Sequence variations, such as alternative polyadenylation of mRNA and single nucleotide polymorphism (SNPs) at miRNA target sites, which may indicate the interaction of miRNA-mediated gene regulation with genetic variations to modulate the MDR phenotype, will be reviewed. Finally, we will highlight novel strategies that could be used to modulate ncRNAs and circumvent ABC transporter-mediated MDR.

利用非编码 RNA 介导的 ATP 结合盒 (ABC) 转运体调控克服癌症化疗的多药耐药性
多药耐药性(MDR)是导致癌症化疗患者治疗失败的主要因素之一。多药耐药性是一种复杂的多因素现象,其特点是多种抗癌药物的疗效降低或减弱,这些药物在结构上和机理上各不相同。ATP结合盒(ABC)转运体,特别是ABCG2和ABCB1的过度表达是癌细胞MDR的主要介质之一,它能促进某些化疗药物从癌细胞中外流,从而降低或取消其疗效。许多研究表明,非编码 RNA(ncRNA),尤其是微 RNA(miRNA)、长非编码 RNA(lncRNA)和环状 RNA(circRNA),在介导某些 MDR 癌细胞中 ABC 转运体的上调方面起着关键作用。本综述将提供有关癌细胞中 ncRNAs 的异常调控诱导 ABC 转运体的最新信息。我们还将讨论各种体液中循环 ncRNA 的测量和生物特征,这些 ncRNA 是预测癌症患者对化疗反应的潜在生物标志物。我们还将回顾mRNA的替代多腺苷酸化和miRNA靶位点的单核苷酸多态性(SNPs)等序列变异,这些变异可能表明miRNA介导的基因调控与遗传变异相互作用,从而调节MDR表型。最后,我们将重点介绍可用于调节 ncRNA 和规避 ABC 转运体介导的 MDR 的新策略。
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来源期刊
Drug Resistance Updates
Drug Resistance Updates 医学-药学
CiteScore
26.20
自引率
11.90%
发文量
32
审稿时长
29 days
期刊介绍: Drug Resistance Updates serves as a platform for publishing original research, commentary, and expert reviews on significant advancements in drug resistance related to infectious diseases and cancer. It encompasses diverse disciplines such as molecular biology, biochemistry, cell biology, pharmacology, microbiology, preclinical therapeutics, oncology, and clinical medicine. The journal addresses both basic research and clinical aspects of drug resistance, providing insights into novel drugs and strategies to overcome resistance. Original research articles are welcomed, and review articles are authored by leaders in the field by invitation. Articles are written by leaders in the field, in response to an invitation from the Editors, and are peer-reviewed prior to publication. Articles are clear, readable, and up-to-date, suitable for a multidisciplinary readership and include schematic diagrams and other illustrations conveying the major points of the article. The goal is to highlight recent areas of growth and put them in perspective. *Expert reviews in clinical and basic drug resistance research in oncology and infectious disease *Describes emerging technologies and therapies, particularly those that overcome drug resistance *Emphasises common themes in microbial and cancer research
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