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.

• Klíčová slova
• DNA methylation, epigenetic therapy, epigenetics, histone modifications, microRNA clusters, microRNA families, tumor development,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Mutation of SMARCA4 (BRG1), the ATPase of BAF (mSWI/SNF) and PBAF complexes, contributes to a range of malignancies and neurologic disorders. Unfortunately, the effects of SMARCA4 missense mutations have remained uncertain. Here we show that SMARCA4 cancer missense mutations target conserved ATPase surfaces and disrupt the mechanochemical cycle of remodeling. We find that heterozygous expression of mutants alters the open chromatin landscape at thousands of sites across the genome. Loss of DNA accessibility does not directly overlap with Polycomb accumulation, but is enriched in 'A compartments' at active enhancers, which lose H3K27ac but not H3K4me1. Affected positions include hundreds of sites identified as superenhancers in many tissues. Dominant-negative mutation induces pro-oncogenic expression changes, including increased expression of Myc and its target genes. Together, our data suggest that disruption of enhancer accessibility represents a key source of altered function in disorders with SMARCA4 mutations in a wide variety of tissues.

• MeSH
• adenosintrifosfatasy metabolismus   MeSH
• chromatin chemie   MeSH
• DNA-helikasy genetika   MeSH
• dominantní geny * MeSH
• epigenomika MeSH
• genotyp MeSH
• heterozygot MeSH
• jaderné proteiny genetika   MeSH
• kultivační média MeSH
• lidé MeSH
• missense mutace MeSH
• multivariační analýza MeSH
• mutace * MeSH
• myší embryonální kmenové buňky cytologie   MeSH
• myši transgenní MeSH
• myši MeSH
• nádory genetika   MeSH
• polycomb proteiny genetika   MeSH
• restrukturace chromatinu MeSH
• sekvenční analýza RNA MeSH
• transkripční faktory genetika   MeSH
• zesilovače transkripce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• adenosintrifosfatasy MeSH
• chromatin MeSH
• DNA-helikasy MeSH
• jaderné proteiny MeSH
• kultivační média MeSH
• polycomb proteiny MeSH
• SMARCA4 protein, human MeSH Prohlížeč
• transkripční faktory MeSH