Gregorova Jana, Vychytilova-Faltejskova Petra, Sevcikova Sabina
Babak Myeloma Group, Department of Pathophysiology, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic.
Department of Molecular Medicine, Central European Institute of Technology (CEITEC), Masaryk University, 625 00 Brno, Czech Republic.
Cancers (Basel). 2021 Mar 16;13(6):1333. doi: 10.3390/cancers13061333.
MicroRNAs are small non-coding single-stranded RNA molecules regulating gene expression on a post-transcriptional level based on the seed sequence similarity. They are frequently clustered; thus, they are either simultaneously transcribed into a single polycistronic transcript or they may be transcribed independently. Importantly, microRNA families that contain the same seed region and thus target related signaling proteins, may be localized in one or more clusters, which are in a close relationship. MicroRNAs are involved in basic physiological processes, and their deregulation is associated with the origin of various pathologies, including solid tumors or hematologic malignancies. Recently, the interplay between the expression of microRNA clusters and families and epigenetic machinery was described, indicating aberrant DNA methylation or histone modifications as major mechanisms responsible for microRNA deregulation during cancerogenesis. In this review, the most studied microRNA clusters and families affected by hyper- or hypomethylation as well as by histone modifications are presented with the focus on particular mechanisms. Finally, the diagnostic and prognostic potential of microRNA clusters and families is discussed together with technologies currently used for epigenetic-based cancer therapies.
微小RNA是一类小的非编码单链RNA分子，它们基于种子序列相似性在转录后水平上调节基因表达。它们常常成簇存在；因此，它们要么同时转录成单个多顺反子转录本，要么可能独立转录。重要的是，包含相同种子区域并因此靶向相关信号蛋白的微小RNA家族，可能定位在一个或多个密切相关的簇中。微小RNA参与基本的生理过程，其失调与包括实体瘤或血液系统恶性肿瘤在内的各种病理状态的发生有关。最近，微小RNA簇和家族的表达与表观遗传机制之间的相互作用被描述，表明异常的DNA甲基化或组蛋白修饰是癌症发生过程中微小RNA失调的主要机制。在这篇综述中，介绍了受高甲基化或低甲基化以及组蛋白修饰影响的研究最多的微小RNA簇和家族，并重点关注了特定机制。最后，讨论了微小RNA簇和家族的诊断和预后潜力以及目前用于基于表观遗传学的癌症治疗的技术。
