Turco Chiara, Donzelli Sara, Fontemaggi Giulia
Oncogenomic and Epigenetic Unit, Department of Diagnostic Research and Technological Innovation, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
Front Cell Dev Biol. 2020 Jun 17;8:427. doi: 10.3389/fcell.2020.00427. eCollection 2020.
The miR-15/107 group of microRNAs (miRNAs) encloses 10 annotated human members and is defined based on the presence of the sequence AGCAGC near the mature miRNAs' 5' end. Members of the miR-15/107 group expressed in humans are highly evolutionarily conserved, and seven of these miRNAs are widespread in vertebrate species. Contrary to the majority of miRNAs, which recognize complementary sequences on the 3'UTR region, some members of the miR-15/107 group are peculiarly characterized by the ability to target the coding sequence (CDS) of their target mRNAs, inhibiting translation without strongly affecting their mRNA levels. There is compelling evidence that different members of the miR-15/107 group regulate overlapping lists of mRNA targets but also show target specificity. The ubiquitously expressed miR-15/107 gene group controls several human cellular pathways, such as proliferation, angiogenesis, and lipid metabolism, and might be altered in various diseases, such as neurodegenerative diseases and cancer. Intriguingly, despite sharing the same seed sequence, different members of this family of miRNAs may behave as oncomiRs or as tumor suppressor miRNAs in the context of cancer cells. This review discusses the regulation and functional contribution of the miR-15/107 group to the control of gene expression. Moreover, we particularly focus on the contribution of specific miR-15/107 group members as tumor suppressors in breast cancer, reviewing literature reporting their ability to function as major controllers of a variety of cell pathways and to act as powerful biomarkers in this disease.
微小RNA(miRNA)中的miR-15/107组包含10个已注释的人类成员,其定义基于成熟miRNA的5'端附近存在序列AGCAGC。在人类中表达的miR-15/107组成员在进化上高度保守,其中7种miRNA在脊椎动物物种中广泛存在。与大多数识别3'UTR区域互补序列的miRNA相反,miR-15/107组的一些成员具有独特的特征,即能够靶向其靶mRNA的编码序列(CDS),在不强烈影响其mRNA水平的情况下抑制翻译。有确凿证据表明,miR-15/107组的不同成员调控重叠的mRNA靶标列表,但也表现出靶标特异性。普遍表达的miR-15/107基因组控制多种人类细胞途径,如增殖、血管生成和脂质代谢,并且可能在各种疾病中发生改变,如神经退行性疾病和癌症。有趣的是,尽管该家族的miRNA共享相同的种子序列,但在癌细胞的背景下,该家族的不同成员可能表现为癌基因miRNA或肿瘤抑制miRNA。本综述讨论miR-15/107组对基因表达控制的调控及其功能贡献。此外,我们特别关注特定miR-15/107组成员作为乳腺癌肿瘤抑制因子的贡献,回顾了报道它们作为多种细胞途径的主要调控因子以及作为该疾病有力生物标志物的功能的文献。