Discovered in 1993, micoRNAs (miRNAs) are now recognized as one of the major regulatory gene families in eukaryotes. To date, 24521 microRNAs have been discovered and there are certainly more to come. It was primarily acknowledged that miRNAs result in gene expression repression at both the level of mRNA stability by conducting mRNA degradation and the level of translation (at initiation and after initiation) by inhibiting protein translation or degrading the polypeptides through binding complementarily to 3′UTR of the target mRNAs. Nevertheless, some studies revealed that miRNAs have the capability of activating gene expression directly or indirectly in respond to different cell types and conditions and in the presence of distinct cofactors. This reversibility in their posttranslational gene regulatory natures enables the bearing cells to rapidly response to different cell conditions and consequently block unnecessary energy wastage or maintain the cell state. This paper provides an overview of the current understandings of the miRNA characteristics including their genes and biogenesis, as well as their mediated downregulation. We also review up-to-date knowledge of miRNA-mediated gene upregulation through highlighting some notable examples and discuss the emerging concepts of their associations with other posttranscriptional gene regulation processes.

The widespread implementation of mass sequencing has revealed a diverse landscape of small RNAs derived from larger precursors. Whilst many of these are likely to be byproducts of degradation, there are nevertheless metabolically stable fragments derived from tRNAs, rRNAs, snoRNAs, and other non-coding RNA, with a number of examples of the production of such fragments being conserved across species. Coupled with specific interactions to RNA-binding proteins and a growing number of experimentally reported examples suggesting function, a case is emerging whereby the biological significance of small non-coding RNAs extends far beyond miRNAs and piRNAs. Related to this, a similarly complex picture is emerging of non-canonical roles for the non-coding precursors, such as for snoRNAs that are also implicated in such areas as the silencing of gene expression and the regulation of alternative splicing. This is in addition to a body of literature describing snoRNAs as an additional source of miRNA-like regulators. This review seeks to highlight emerging roles for such non-coding RNA, focusing specifically on “new” roles for snoRNAs and the small fragments derived from them.

Diet-derived histone deacetylase inhibitor (HDACi), butyrate, alters global acetylation and consequently global gene expression in colorectal cancer (CRC) cells to exert its anticancer effects. Aberrant microRNA (miRNA) expression contributes to CRC development and progression. Butyrate-mediated modulation of microRNA (miRNA) expression remains under-investigated. This study employed a systems biology approach to gain a comprehensive understanding of the complex miRNA-mRNA interactions contributing to the butyrate response in CRC cells. Next-generation sequencing, gene ontology (GO) and pathway enrichment analyses were utilized to reveal the extent of butyrate-mediated gene regulation in CRC cells. Changes in cell proliferation, apoptosis, the cell cycle and gene expression induced by miRNAs and target gene knockdown in CRC cells were assessed. Butyrate induced differential expression of 113 miRNAs and 2447 protein-coding genes in HCT116 cells. Butyrate also altered transcript splicing of 1589 protein-coding genes. GO, and pathway enrichment analyses revealed the cell cycle to be a central target of the butyrate response. Two butyrate-induced miRNAs, miR-139 and miR-542, acted cooperatively with butyrate to induce apoptosis and reduce CRC cell proliferation by regulating target genes, including cell cycle-related EIF4G2 and BIRC5. EIF4G2 RNA interference mimicked the miR-139-mediated reduction in cell proliferation. The cell cycle is a critical pathway involved in the butyrate response of CRC cells. These findings reveal novel roles for miRNAs in the cell cycle-related, anticancer effects of butyrate in CRC cells.