Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany.
Fraunhofer Institute for Translational Medicine and Pharmacology, 60596 Frankfurt, Germany.
Int J Mol Sci. 2022 Apr 19;23(9):4493. doi: 10.3390/ijms23094493.
MicroRNAs have been projected as promising tools for diagnostic and prognostic purposes in cancer. More recently, they have been highlighted as RNA therapeutic targets for cancer therapy. Though miRs perform a generic function of post-transcriptional gene regulation, their utility in RNA therapeutics mostly relies on their biochemical nature and their assembly with other macromolecules. Release of extracellular miRs is broadly categorized into two different compositions, namely exosomal (extracellular vesicles) and non-exosomal. This nature of miRs not only affects the uptake into target cells but also poses a challenge and opportunity for RNA therapeutics in cancer. By virtue of their ability to act as mediators of intercellular communication in the tumor microenvironment, extracellular miRs perform both, depending upon the target cell and target landscape, pro- and anti-tumor functions. Tumor-derived miRs mostly perform pro-tumor functions, whereas host cell- or stroma-derived miRs are involved in anti-tumor activities. This review deals with the recent understanding of exosomal and non-exosomal miRs in the tumor microenvironment, as a tool for pro- and anti-tumor activity and prospective exploit options for cancer therapy.
微小 RNA 被认为是癌症诊断和预后的有前途的工具。最近，它们被强调为癌症治疗的 RNA 治疗靶点。尽管 miR 执行通用的转录后基因调控功能，但它们在 RNA 治疗中的应用主要依赖于它们的生化性质及其与其他大分子的组装。细胞外 miR 的释放广泛分为两种不同的成分，即外泌体（细胞外囊泡）和非外泌体。miR 的这种性质不仅影响到靶细胞的摄取，而且对癌症的 RNA 治疗提出了挑战和机遇。由于其能够在肿瘤微环境中充当细胞间通讯的介质，细胞外 miR 具有双重作用，取决于靶细胞和靶标景观，具有促进和抗肿瘤功能。肿瘤来源的 miR 主要发挥促肿瘤作用，而宿主细胞或基质衍生的 miR 参与抗肿瘤活性。本文综述了肿瘤微环境中外泌体和非外泌体 miR 的最新研究进展，作为促进和抗肿瘤活性的工具，以及癌症治疗的潜在利用选择。
