Epigenetic Regulation of MicroRNA Clusters and Families during Tumor Development

Abstract

MicroRNAs are small non-coding single-stranded RNA molecules regulating gene expression on a posttranscriptional 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.

miR-294 and miR-410 Negatively Regulate Tnfa, Arginine Transporter Cat1/2, and Nos2 mRNAs in Murine Macrophages Infected with Leishmania amazonensis

“…Indeed, miR-301b is associated with NF-κB activity inhibiting p65 nuclear translocation in pancreatic Panc-1 and BxPC-3 cell lines, interfering with LPS signals, and corroborating the involvement of these miRNAs in the regulation of inflammation [57], which is implicated in TNF and NOS2 expression. Intriguingly, miR-130b/miR-301b belongs to the same cluster family, sharing target genes and cell proliferation with prostate cancer [58]. miR-301b inhibition did not interfere in the Tnfa transcripts even though miR-301b shares the same seed as Tnfa 3 UTR does with miR-294, which is probably because it acts in a different way in the absence of miR-294.…”

spongEffects: ceRNA modules offer patient-specific insights into the miRNA regulatory landscape

“…Focusing on the miRNA expression differences between subtypes offers a potential explanation for the spongEffects scores we have observed here. a) miR-17~92-1 cluster, mir-106a~363 cluster Gregorova et al proposed that the miR-17~92-1 and mir-106a~363 clusters should be considered together since they are frequently upregulated in solid tumors and hematologic malignancies [68,69]. We can see a significant visual collection around hsa-miR-18a-5p.…”

“…These miRNAs are as a whole or as a part involved in a large part of the ceRNA interactions in 10 of the 25 modules: ALDH1L1-AS2, TPM1-AS, ENSG00000258535, TMEM26-AS1, ENSG00000229425, BACH1-AS1, LINC00663, ENSG00000225498, CACNA1G-AS1, and DNM3OS. Gregorova et al described the miR-130-3p/301-3p/454-3p family as significant in cancer biology [69]. hsa-miR-130b-3p was confirmed to directly target colony-stimulating factor 1 (CSF-1), downregulate CSF-1 expression, and result in decreased sensitivity to anticancer drugs [74].…”

Molecular Mechanisms of Nutrient-Mediated Regulation of MicroRNAs in Pancreatic β-cells

“…As is the case for messenger RNAs, the transcription of each pri-miRNA is tightly controlled by epigenetic and transcription factors. Epigenetic regulation of miRNA expression has been widely studied in tumours and involves DNA methylation and histone modifications that often contribute to miRNA dysregulation during tumour progression ( 182 ). It is well established that miRNAs form tightly coordinated regulatory networks with transcription factors, which contribute to reinforce cellular states ( 47 ).…”