Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
IUBMB Life. 2024 Nov;76(11):883-921. doi: 10.1002/iub.2888. Epub 2024 Aug 1.
Cancer drug resistance poses a significant obstacle to successful chemotherapy, primarily driven by the activity of ATP-binding cassette (ABC) transporters, which actively efflux chemotherapeutic agents from cancer cells, reducing their intracellular concentrations and therapeutic efficacy. Recent studies have highlighted the pivotal role of long noncoding RNAs (lncRNAs) in regulating this resistance, positioning them as crucial modulators of ABC transporter function. lncRNAs, once considered transcriptional noise, are now recognized for their complex regulatory capabilities at various cellular levels, including chromatin modification, transcription, and post-transcriptional processing. This review synthesizes current research demonstrating how lncRNAs influence cancer drug resistance by modulating the expression and activity of ABC transporters. lncRNAs can act as molecular sponges, sequestering microRNAs that would otherwise downregulate ABC transporter genes. Additionally, they can alter the epigenetic landscape of these genes, affecting their transcriptional activity. Mechanistic insights reveal that lncRNAs contribute to the activity of ABC transporters, thereby altering the efflux of chemotherapeutic drugs and promoting drug resistance. Understanding these interactions provides a new perspective on the molecular basis of chemoresistance, emphasizing the regulatory network of lncRNAs and ABC transporters. This knowledge not only deepens our understanding of the biological mechanisms underlying drug resistance but also suggests novel therapeutic strategies. In conclusion, the intricate interplay between lncRNAs and ABC transporters is crucial for developing innovative solutions to combat cancer drug resistance, underscoring the importance of continued research in this field.
癌症耐药性是化疗成功的主要障碍,主要归因于 ATP 结合盒(ABC)转运蛋白的活性,其可将化疗药物从癌细胞中主动排出,降低其细胞内浓度和治疗效果。最近的研究强调了长非编码 RNA(lncRNA)在调节这种耐药性方面的关键作用,将其定位为 ABC 转运蛋白功能的重要调节剂。lncRNA 曾经被认为是转录噪声,但现在已被认识到其在各种细胞水平上具有复杂的调节能力,包括染色质修饰、转录和转录后加工。本综述综合了当前的研究成果,展示了 lncRNA 通过调节 ABC 转运蛋白的表达和活性来影响癌症耐药性的机制。lncRNA 可以作为分子海绵,结合原本会下调 ABC 转运蛋白基因的 microRNA。此外,它们还可以改变这些基因的表观遗传景观,影响其转录活性。机制研究表明,lncRNA 有助于 ABC 转运蛋白的活性,从而改变化疗药物的外排,促进耐药性的发生。了解这些相互作用为化学耐药性的分子基础提供了新的视角,强调了 lncRNA 和 ABC 转运蛋白的调节网络。这一知识不仅加深了我们对耐药性背后生物学机制的理解,还为开发创新的治疗策略提供了依据。总之,lncRNA 和 ABC 转运蛋白之间的复杂相互作用对于开发克服癌症耐药性的创新解决方案至关重要,突显了该领域持续研究的重要性。