The microRNA miR-155 is prominent in cancer biology. Among microRNAs that have been linked to cancer, it is the most commonly overexpressed in malignancies (PNAS 109:20047-20052, 2012). Since its discovery, miR-155 has been implicated in promoting cancers of the breast, lung, liver, and lymphatic system. As such, targeted therapies may prove beneficial to cancer treatment. This review discusses the important role of miR-155 in oncogenesis. It synthesizes information from ten recent papers on miR-155, and includes an analysis and discussion of its association with cancer, interactions with other miRNAs, mechanisms of action, and the most promising available treatment options.Current debates in the field include the importance of miRNAs in general and their utility as targets in preventing tumorigenesis (Blood 119:513-520, 2012). Most of the papers being reviewed here confirm the role of miR-155 in oncogenesis (EMBO Mol Med 1:288-295, 2009). While there is some controversy surrounding recent research that claims that miR-155 may display anti-oncogenic or pro-immunological benefits (Cell Rep 2:1697–1709, 2012), most research seems to point to the importance of anti-miRs, with anti-miR-155 in particular, for cancer therapy.

BackgroundStructured noncoding RNAs (ncRNAs) play essential roles in many biological processes such as gene regulation, signaling, RNA processing, and protein synthesis. Among the most common groups of ncRNAs in bacteria are riboswitches. These cis-regulatory, metabolite-binding RNAs are present in many species where they regulate various metabolic and signaling pathways. Collectively, there are likely to be hundreds of novel riboswitch classes that remain hidden in the bacterial genomes that have already been sequenced, and potentially thousands of classes distributed among various other species in the biosphere. The vast majority of these undiscovered classes are proposed to be exceedingly rare, and so current bioinformatics search techniques are reaching their limits for differentiating between true riboswitch candidates and false positives.ResultsHerein, we exploit a computational search pipeline that can efficiently identify intergenic regions most likely to encode structured ncRNAs. Application of this method to five bacterial genomes yielded nearly 70 novel genetic elements including 30 novel candidate ncRNA motifs. Among the riboswitch candidates identified is an RNA motif involved in the regulation of thiamin biosynthesis.ConclusionsAnalysis of other genomes will undoubtedly lead to the discovery of many additional novel structured ncRNAs, and provide insight into the range of riboswitches and other kinds of ncRNAs remaining to be discovered in bacteria and archaea.Electronic supplementary materialThe online version of this article (10.1186/s12866-019-1433-7) contains supplementary material, which is available to authorized users.

A bacterial noncoding RNA motif almost exclusively associated with pnuC genes was uncovered using comparative sequence analysis. Some PnuC proteins are known to transport nicotinamide riboside (NR), which is a component of the ubiquitous and abundant enzyme cofactor nicotinamide adenine dinucleotide (NAD +). Thus, we speculated that the newly found 'pnuC motif' RNAs might function as aptamers for a novel class of NAD +sensing riboswitches. RNA constructs that encompass the conserved nucleotides and secondary structure features that define the motif indeed selectively bind NAD + , nicotinamide mononucleotide (NMN), and NR. Mutations that disrupt strictly conserved nucleotides of the aptamer also disrupt ligand binding. These bioinformatic and biochemical findings indicate that pnuC motif RNAs are likely members of a second riboswitch class that regulates gene expression in response to NAD + binding.

Comparative sequence analysis methods are highly effective for uncovering novel classes of structured noncoding RNAs (ncRNAs) from bacterial genomic DNA sequence datasets. Previously, we developed a computational pipeline to more comprehensively identify structured ncRNA representatives from individual bacterial genomes. This search process exploits the fact that genomic regions serving as templates for the transcription of structured RNAs tend to be present in longer than average noncoding 'intergenic regions' (IGRs) that are enriched in G and C nucleotides compared to the remainder of the genome. In the present study, we apply this computational pipeline to identify structured ncRNA candidates from 26 diverse bacterial species. Numerous novel structured ncRNA motifs were discovered, including several riboswitch candidates, one whose ligand has been identified and others that have yet to be experimentally validated. Our findings support recent predictions that hundreds of novel riboswitch classes and other ncRNAs remain undiscovered among the limited number of bacterial species whose genomes have been completely sequenced.

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