Department of Genetics, Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, 30-705 Krakow, Poland.
Biomolecules. 2020 Sep 7;10(9):1285. doi: 10.3390/biom10091285.
Usually, miRNAs function post-transcriptionally, by base-pairing with the 3'UTR of target mRNAs, repressing protein synthesis in the cytoplasm. Furthermore, other regions including gene promoters, as well as coding and 5'UTR regions of mRNAs are able to interact with miRNAs. In recent years, miRNAs have emerged as important regulators of both translational and transcriptional programs. The expression of miRNA genes, similar to protein-coding genes, can be epigenetically regulated, in turn miRNA molecules (named epi-miRs) are able to regulate epigenetic enzymatic machinery. The most recent line of evidence indicates that miRNAs can influence physiological processes, such as embryonic development, cell proliferation, differentiation, and apoptosis as well as pathological processes (e.g., tumorigenesis) through epigenetic mechanisms. Some tumor types show repression of tumor-suppressor epi-miRs resulting in cancer progression and metastasis, hence these molecules have become novel therapeutic targets in the last few years. This review provides information about miRNAs involvement in the various levels of transcription and translation regulation, as well as discusses therapeutic potential of tumor-suppressor epi-miRs used in in vitro and in vivo anti-cancer therapy.
通常情况下,miRNA 通过与靶 mRNA 的 3'UTR 碱基配对,在细胞质中抑制蛋白质合成,从而发挥转录后功能。此外,其他区域包括基因启动子以及 mRNA 的编码区和 5'UTR 区域也能够与 miRNA 相互作用。近年来,miRNA 已成为翻译和转录程序的重要调控因子。miRNA 基因的表达与蛋白质编码基因类似,可以受到表观遗传调控,反过来,miRNA 分子(称为 epi-miRs)能够调节表观遗传酶机制。最新的证据表明,miRNA 可以通过表观遗传机制影响生理过程(如胚胎发育、细胞增殖、分化和凋亡)以及病理过程(如肿瘤发生)。一些肿瘤类型表现出肿瘤抑制 epi-miR 的抑制,导致癌症的进展和转移,因此这些分子在过去几年中已成为新的治疗靶点。本文综述了 miRNA 在转录和翻译调控各个层面的作用,并讨论了肿瘤抑制 epi-miR 在体外和体内抗癌治疗中的治疗潜力。