外泌体miRNA治疗多发性骨髓瘤的作用与机制  

Effects and mechanisms of exosomal miRNA in treatment of multiple myeloma

作　　者：赵艺涵 孙旭杭 赵琳[3] 蒋士卿[1] Zhao Yihan;Sun Xuhang;Zhao Lin;Jiang Shiqing(Department of Hematology and Oncology,First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000,Henan Province,China;School of First Clinical Medicine,Henan University of Chinese Medicine,Zhengzhou 450000,Henan Province,China;Department of Hematology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200000,China)

机构地区：[1]河南中医药大学第一附属医院血液肿瘤科,河南省郑州市450000 [2]河南中医药大学第一临床医学院,河南省郑州市450000 [3]上海中医药大学附属曙光医院血液科,上海市200000

出　　处：《中国组织工程研究》2025年第31期6743-6752,共10页Chinese Journal of Tissue Engineering Research

基　　金：国家中医药管理局联合开放课题“张仲景传承与创新专项”(GZY-KJS-2022-038-2),项目负责人:蒋士卿;河南省自然科学基金项目面上项目(202300420055),项目负责人:蒋士卿;河南省中医药科学研究重大专项课题(2024ZYZD03),项目负责人:蒋士卿;河南中医药大学研究生科研创新类项目(2023KYCX003),项目负责人:赵艺涵。

摘　　要：背景:多发性骨髓瘤是最常见的血液恶性肿瘤之一,具有难治疗、易复发、易耐药的特点,至今仍无法治愈。外泌体的内源性转运系统通过影响细胞间功能成分的交换而发挥通讯作用,其中miRNA因尺寸微小更容易被包装在外泌体内,故影响细胞功能的途径多、范围广。目的:归纳并总结多发性骨髓瘤中外泌体miRNA发挥作用的机制,提出潜在靶点。方法:以“multiple myeloma,bone marrow mesenchyml stem cell,fibroblasts,peripheral blood,complication,progression,drug resistance,exosomal miRNA”为英文关键检索词,检索PubMed数据库的相关文献。文献检索时限为数据库建库至2024年6月。通过阅读文题和摘要进行初筛,排除无关或内容重复或无参考意义的文献,最后纳入81篇文献进行综述。结果与结论:①多发性骨髓瘤细胞通过各种miRNA介导的外泌体调节成骨和破骨功能平衡参与多发性骨髓瘤骨病变、调控红细胞钙离子外排通道参与高钙血症的发生、促进肾上皮-间充质转化引发肾纤维化和肾功能不全、上调骨髓来源的单核抑制细胞促进免疫微环境的抑制;此外,多发性骨髓瘤细胞外泌体miRNA还参与了免疫治疗耐药的发生和发展以及血管生成、细胞增殖及细胞衰老等病理过程。②骨髓间充质干细胞和肿瘤相关成纤维细胞均可通过外泌体miRNA影响多发性骨髓瘤细胞的增殖、转移和凋亡,干预血管生成,调控化疗药物的耐药性。③外周血循环外泌体miRNA作为前沿的无创生物标志物,可发挥判断多发性骨髓瘤病程分期和进展,预测患者生存及预后,评估药物敏感性和耐药性等关键作用。④多发性骨髓瘤外泌体长链非编码RNA、环状RNA、miRNA及mRNA,靶基因多种研究因素可形成不同的组合,灵活地构建新型生物轴和生物分子网络,符合整体医学的发展理念。⑤外泌体miRNA作为预测生物标志物及新药研发的治疗靶点具有�BACKGROUND:Multiple myeloma is one of the most common hematological malignancies,which is difficult to treat,prone to relapse,and resistant to drugs.The endogenous transport system of exosomes plays a communication role by affecting the exchange of functional components between cells.Among them,miRNA is more easily packaged in exosomes due to its small size,so it affects cell function in many ways and over a wide range.OBJECTIVE:To summarize the mechanism of exosomal miRNA in multiple myeloma and to propose potential targets.METHODS:The terms“multiple myeloma,bone marrow mesenchyml stem cell,fibroblasts,peripheral blood,complication,progression,drug resistance,exosomal miRNA”were used as English search terms in the PubMed database.The time frame of the search was from the inception to June 2024.After reading the titles and abstracts,we excluded irrelevant or repetitive literature,and finally included 81 papers for review.RESULTS AND CONCLUSION:(1)Multiple myeloma cells participate in multiple myeloma bone lesions by regulating the balance of osteogenic and osteoclast functions through various miRNA mediated exosomes,regulating erythrocyte calcium ion efflux channels to participate in the occurrence of hypercalcemia,promoting renal epithelial mesenchymal transition leading to renal fibrosis and renal dysfunction,and upregulating bone marrow-derived mononuclear suppressor cells to promote suppression of the immune microenvironment.In addition,miRNAs in the exosomes of multiple myeloma cells are also involved in the occurrence and development of immunotherapy resistance,as well as pathological processes such as angiogenesis,cell proliferation,and cell aging.(2)Both bone marrow mesenchymal stem cells and tumor-associated fibroblasts can affect the proliferation,metastasis,and apoptosis of multiple myeloma cells through exosomal miRNA,interfere with angiogenesis,and regulate the resistance of chemotherapy drugs.(3)Peripheral blood circulating exosomal miRNAs,as cutting-edge noninvasive biomarkers,can play a key ro

关 键 词：多发性骨髓瘤 进展 耐药 并发症 骨髓间充质干细胞 成纤维细胞 外周血 外泌体 MIRNA 

分 类 号：R459.9[医药卫生—治疗学] R363[医药卫生—临床医学] R733.3