外泌体miRNA参与肿瘤化疗耐药的机制

Mechanism of exosomal miRNA involved in tumor chemotherapy resistance

背景:化疗作为癌症治疗的常见手段,前期具有一定的治疗效果,但随着化疗次数增加,肿瘤细胞对药物的抵抗性也逐渐增加,即化疗耐药性。目前化疗耐药性产生的主要机制包括化疗药物未能达到肿瘤部位,药物活性丧失导致药效下降,肿瘤细胞通过重塑代谢功能、基因表型和微环境逃避药物攻击等,但具体机制还有待深入探讨。目的:归纳并总结不同肿瘤中外泌体miRNA参与耐药的机制,提出潜在靶点。方法:以“hematological malignancies,liver cancer,lung cancer,breast cancer,melanoma,colorectal cancer,drug resistance,exosomal miRNAs”为英文检索词,检索PubMed数据库。检索时间范围为2013年1月至2023年8月。通过阅读文题和摘要进行初步筛选,排除与此次研究内容相关性差或内容重复的文献,最后纳入60篇文献进行综述。结果与结论:(1)外泌体miRNA进入细胞间质和循环,通过发挥局部旁分泌或远端效应,参与不同肿瘤生物进程的形成和发展,包括肿瘤微环境重塑、血管生成和耐药性产生;(2)外泌体miRNA可以透过细胞膜进入另一个细胞的胞浆内,通过传递miRNA启动或抑制受体细胞中的信号通路,在化疗过程中维持细胞存活、增殖和转移能力,从而导致耐药产生;(3)目前已经鉴定出许多与化疗耐药有关的外泌体miRNA,并将其作为常见肿瘤治疗靶点来开展研究;(4)虽然外泌体miRNA作为潜在的生物标志物和治疗靶点具有很大的前景,但仍有一些研究缺陷需要解决:一是缺乏用于外泌体分离和表征的标准化方案,导致不同研究中使用的方法存在差异;二是虽然外泌体中miRNA的存在和丰度已被广泛研究,但其功能作用和作用机制尚不完全清楚,阐明外泌体miRNA调控的特定靶点和途径可以为它们的生物学意义和潜在的治疗应用提供有价值的见解。解决这些研究缺陷将有助于更全面了解外泌体miRNA及其在各个领域的潜在应用,包括诊断、治疗和个性化医疗。

BACKGROUND:As a common method of cancer treatment,chemotherapy has a certain therapeutic effect in the early stage.However,as the frequency of chemotherapy increases,the resistance of tumor cells to drugs gradually increases,that is,chemotherapy resistance.At present,the main mechanisms of chemotherapy resistance include the failure of chemotherapy drugs to reach the tumor site,the loss of drug activity leading to a decrease in drug efficacy,and tumor cells evading drug attack by reshaping their metabolic functions,gene phenotypes,and microenvironment.However,the specific mechanism remains to be discussed in depth.OBJECTIVE:To summarize the mechanisms by which exosomal miRNA is involved in drug resistance in different tumors,and to propose potential targets.METHODS:The PubMed database was searched using the English search terms“hematological malignancies,liver cancer,lung cancer,breast cancer,melanoma,colorectal cancer,drug resistance,exosomal miRNAs.”The search time range was from January 2013 to August 2023.Preliminary screening was carried out by reading the titles and abstracts,and the exclusion criteria were for literature with poor relevance to the research content or repetitive content.Finally,60 articles were included for review.RESULTS AND CONCLUSION:(1)Exosomal miRNA enters the intercellular matrix and circulation,and participates in the formation and development of different tumor biological processes,including tumor microenvironment remodeling,angiogenesis,and drug resistance,by exerting local paracrine or distal effects.(2)Exosomal miRNA can penetrate the cell membrane into the cytoplasm of another cell,activate or inhibit the signaling pathway in the recipient cell by delivering miRNA,and maintain cell survival,proliferation,and metastasis during chemotherapy,thus leading to drug resistance.(3)Many exosomal miRNAs related to chemotherapy resistance have been identified and studied as common tumor treatment targets.(4)Although exosomal miRNA holds great promise as potential biomarkers and therapeutic targets,there are still some research deficiencies that need to be addressed:Firstly,there is a lack of standardized protocols for exosome isolation and characterization,resulting in differences in the methods used in different studies;secondly,although the presence and abundance of miRNAs in exosomes have been widely studied,their functional roles and mechanisms are not completely clear.Elucidating the specific targets and pathways regulated by exosomal can provide valuable insights into their biological significance and potential therapeutic applications.Addressing these research gaps will contribute to a more comprehensive understanding of exosomal miRNAs and their potential applications in various fields,including diagnosis,therapy,and personalized medicine.