Program of Innovative Cancer Therapeutics, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang Province, China.
Key Laboratory of Organ Transplantation, Hangzhou, 310003, Zhejiang Province, China.
Clin Epigenetics. 2019 Feb 11;11(1):25. doi: 10.1186/s13148-018-0587-8.
MicroRNAs (miRNAs) are small non-coding RNAs with a length of about 19-25 nt, which can regulate various target genes and are thus involved in the regulation of a variety of biological and pathological processes, including the formation and development of cancer. Drug resistance in cancer chemotherapy is one of the main obstacles to curing this malignant disease. Statistical data indicate that over 90% of the mortality of patients with cancer is related to drug resistance. Drug resistance of cancer chemotherapy can be caused by many mechanisms, such as decreased antitumor drug uptake, modified drug targets, altered cell cycle checkpoints, or increased DNA damage repair, among others. In recent years, many studies have shown that miRNAs are involved in the drug resistance of tumor cells by targeting drug-resistance-related genes or influencing genes related to cell proliferation, cell cycle, and apoptosis. A single miRNA often targets a number of genes, and its regulatory effect is tissue-specific. In this review, we emphasize the miRNAs that are involved in the regulation of drug resistance among different cancers and probe the mechanisms of the deregulated expression of miRNAs. The molecular targets of miRNAs and their underlying signaling pathways are also explored comprehensively. A holistic understanding of the functions of miRNAs in drug resistance will help us develop better strategies to regulate them efficiently and will finally pave the way toward better translation of miRNAs into clinics, developing them into a promising approach in cancer therapy.
微小 RNA(miRNA)是一种长度约为 19-25nt 的小型非编码 RNA,可调节各种靶基因,从而参与多种生物和病理过程的调节,包括癌症的形成和发展。癌症化疗中的耐药性是治愈这种恶性疾病的主要障碍之一。统计数据表明,超过 90%的癌症患者的死亡率与耐药性有关。癌症化疗耐药性可能由多种机制引起,例如抗肿瘤药物摄取减少、药物靶标改变、细胞周期检查点改变或 DNA 损伤修复增加等。近年来,许多研究表明,miRNA 通过靶向耐药相关基因或影响与细胞增殖、细胞周期和细胞凋亡相关的基因参与肿瘤细胞的耐药性。单个 miRNA 通常靶向多个基因,其调节作用具有组织特异性。在这篇综述中,我们强调了不同癌症中涉及调节耐药性的 miRNA,并探讨了 miRNA 表达失调的机制。还全面探讨了 miRNA 的分子靶标及其潜在信号通路。全面了解 miRNA 在耐药性中的功能将有助于我们开发出更有效的调节它们的策略,并最终为 miRNA 向临床的更好转化铺平道路,使其成为癌症治疗的一种很有前途的方法。