McCarthy Elan C, Dwyer Róisín M
School of Medicine, Lambe Institute for Translational Research, National University of Ireland Galway, H91 V4AY Galway, Ireland.
Science Foundation Ireland (SFI) Research Centre for Medical Devices (CÚRAM), National University of Ireland Galway, H91 W2TY Galway, Ireland.
Biomedicines. 2021 Jul 16;9(7):827. doi: 10.3390/biomedicines9070827.
Many microRNAs exist in clusters that share comparable sequence homology and may target genes in a common pathway. The miR-379/miR-656 (C14MC) cluster is imprinted in the DLK1-Dio3 region of 14q32.3 and contains 42 miRNAs. It plays a functional role in numerous biological pathways including vascular remodeling and early development. With many C14MC miRNAs highlighted as potential tumor suppressors in a variety of cancers, the role of this cluster in breast cancer (BC) has garnered increased attention in recent years. This review focuses on C14MC in BC, providing an overview of the constituent miRNAs and addressing each in terms of functional impact, potential target genes/pathways, and, where relevant, biomarker capacity. Studies have revealed the regulation of key factors in disease progression and metastasis including tyrosine kinase pathways and factors critical to epithelial-mesenchymal transition (EMT). This has potentially important clinical implications, with EMT playing a critical role in BC metastasis and tyrosine kinase inhibitors (TKIs) in widespread use for the treatment of BC. While the majority of studies have reported tumor-suppressing roles for these miRNAs, some have highlighted their potential as oncomiRs. Understanding the collective contribution of miRNAs within C14MC to BC may support improved understanding of disease etiology and present novel approaches to targeted therapy.
许多微小RNA以簇的形式存在，这些簇具有可比的序列同源性，并且可能靶向共同途径中的基因。miR-379/miR-656（C14MC）簇在14q32.3的DLK1-Dio3区域印记，包含42个微小RNA。它在包括血管重塑和早期发育在内的众多生物学途径中发挥功能作用。由于许多C14MC微小RNA在多种癌症中被视为潜在的肿瘤抑制因子，近年来该簇在乳腺癌（BC）中的作用受到了越来越多的关注。本综述聚焦于乳腺癌中的C14MC，概述其组成的微小RNA，并从功能影响、潜在靶基因/途径以及相关的生物标志物能力方面进行阐述。研究揭示了疾病进展和转移中的关键因子调控，包括酪氨酸激酶途径和上皮-间质转化（EMT）的关键因子。这具有潜在的重要临床意义，因为EMT在乳腺癌转移中起关键作用，而酪氨酸激酶抑制剂（TKIs）广泛用于乳腺癌治疗。虽然大多数研究报道了这些微小RNA的肿瘤抑制作用，但也有一些研究强调了它们作为致癌微小RNA的潜力。了解C14MC内微小RNA对乳腺癌的共同作用可能有助于更好地理解疾病病因，并为靶向治疗提供新方法。
