外泌体非编码RNA在胶质瘤发生发展中的作用及其临床应用前景

Role and clinical application prospects of exosomal non-coding RNAs in the occurrence and development of glioma

背景:恶性神经胶质瘤经过手术、放疗和化疗后,其预后仍然很差,因此阐明胶质瘤发生发展的分子机制,进一步探索可靠的生物标志物至关重要。非编码RNA在外泌体中富集且稳定,由于其在各种肿瘤的起始和进展中的调节功能而受到了广泛关注。目的:文章就外泌体非编码RNA在胶质瘤中的研究和进展进行概述,介绍外泌体非编码RNA的生物来源,阐明其在胶质瘤中的生物学影响,寻找可靠的肿瘤标志物,以期为神经胶质瘤的诊断和治疗提供新的思路。方法:以“Exosome,Extracellular vesicles,Noncoding RNA,Glioma,Molecule mechanism,Biomarkers”为英文检索词,在PubMed和Web of Science数据库中检索筛选出114篇文献进行归纳总结,文献内容主要涉及外泌体非编码RNA在胶质瘤中的肿瘤细胞增殖、侵袭和血管生成,以及外泌体非编码RNA在胶质瘤中的基因诊断和基因治疗等相关内容。结果与结论:①外泌体非编码RNA在细胞间选择性包装、分泌和转移,参与肿瘤微环境中的细胞间通讯,并可调节胶质瘤的许多生物学行为,如增殖、侵袭、血管生成、免疫逃逸和治疗耐药性,在胶质瘤的发生发展中起着重要作用。②外泌体包含多种功能分子,可以反映整个肿瘤复杂的异质性。③外泌体具有较高的特异性和灵敏度,并且非常稳定,在几乎所有类型的体液中都很容易获得,这些因素使外泌体成为最有潜力的生物标记物,这为未来诊断胶质瘤提供了很大帮助。④外泌体是天然且无毒性的,与质膜的构造相当类似,可将其作为许多治疗性药物的治疗载体,携带多种生物活性分子并能轻易跨越血脑屏障,通过外泌体来开发靶向抗癌药物,既能突破血脑屏障,还能避免人体的免疫排斥反应。⑤外泌体与靶细胞结合具有特定的靶向性,这些优势极大提升了外泌体应用在胶质瘤生物靶向治疗的可行性,但其在临床应用中还面临着一些困难,如外泌体的分选难度大,外泌体非编码RNA的含量有限,以及如何让外泌体精确到达肿瘤部位等。⑥随着外泌体非编码RNA在胶质瘤中研究的不断深入,未来将为攻克胶质瘤这一难题提供新的路径。

BACKGROUND:The prognosis of malignant glioma is still poor after surgery,radiotherapy and chemotherapy.Therefore,it is important to clarify the molecular mechanism of glioma development and further explore reliable biomarkers.Non-coding RNAs are enriched and stable in exosomes,and have attracted extensive attention due to their regulatory functions in the initiation and progression of various tumors.OBJECTIVE:To summarize the research and progress of exosomal non-coding RNA in glioma,introduce the biological sources of exosomal non-coding RNA,elucidate its biological effects in glioma,search for reliable tumor markers,and provide new ideas for the diagnosis and treatment of glioma.METHODS:Using“exosome,extracellular vesicles,noncoding RNA,glioma,molecule mechanism,biomarkers”as English search terms,114 articles were searched and summarized in PubMed and Web of Science databases,mainly involving tumor cell proliferation,invasion and angiogenesis of exosomal noncoding RNA in glioma,as well as gene diagnosis and gene therapy of exosomal non-coding RNA in glioma.RESULTS AND CONCLUSION:(1)Exosomal non-coding RNA selectively packages,secretes and metastases between cells,participates in intercellular communication in tumor microenvironment,and regulates many biological behaviors of gliomas,such as proliferation,invasion,angiogenesis,immune escape and therapeutic drug resistance,which plays an important role in the occurrence and development of gliomas.(2)Exosomes contain a variety of functional molecules,which can reflect the complex heterogeneity of the tumor.(3)Exosomes have higher specificity and sensitivity,and are very stable,and can be easily obtained in almost all types of body fluids.These factors make exosomes become the most potential biomarkers,which will be of great help for the diagnosis of gliomas in the future.(4)Exosomes are natural and non-toxic,which are quite similar to the structure of plasma membrane.It can be used as a therapeutic carrier for many therapeutic drugs,carry a variety of bioactive molecules and can easily cross the blood-brain barrier.Through exosomes to develop targeted anti-glioma drugs,it can not only break through the blood-brain barrier,but also avoid immune rejection.(5)The combination of exosomes and target cells has specific targeting,which greatly improves the feasibility of biological targeted therapy,but there are still some difficulties in clinical application,such as the difficulty of sorting exosomes,the limited content of exosomal non-coding RNA,and how to make exocrine reach the tumor site accurately.(6)With the further study of exosomal non-coding RNA in glioma,it will provide a new way to overcome the problem of glioma in the future.