MicroRNA - Volume 6, Issue 3, 2017

Background: Migraine is a prevalent neurovascular disorders with a complex pathophysiology and therapeutic options characterized by important side effects or problems related to drug abuse. No specific biomarkers are recognized to be univocal for this subclinical condition, yet. In this concern microRNAs (miRNAs) have been suggested as potentially useful screening/diagnostic tool, and research is underway to recognize the most effective candidate(s). In this concern in the present review we Herein we highlighted miRs involvement in pain and migraine, as well as drug response and efficacy focusing also on miRs panel results from mice model with multiple induced pain conditions, and human patients with migraine in order to understand if there are similar miRs expression pattern may useful into human translational studies. Results: During human migraine attack specific miRs were found dysregulated, as well as in mouse models with different pain conditions. Amongst all the miRs screened in mice/human suffering of pain the miR-590-5p was found alterated. This latter miR, in mice is modulated by celecoxib, while in human is dysregulated in the complex regional pain syndrome, condition where migraine assume a risk factor for its development. Recently has been reported that pharmacological treatments, indirectly can pertubate miRNA expression results. Therefore, miR-590-5p could assume an interesting double meaning for a clinical point of view. It can be considered biomarker of general pain, including migraine and also biomarker to evaluate the efficacy of the drug treatment. This could be of great importance in infant-juvenile segment, where the diagnosis of migraine is very challenging. In this view, since therapy is often started with NSAIDs herein we discuss also how the discovery of the new role of miRNAs in determining drug efficacy open a new scenario in the pain-migraine tailored therapy and pharmacogenomics concept. Conclusion: miRNAs could have a pleiotropic meaning in the clinical management of migraine and could represent biomarkers of pathology, of drug efficacy as well as drug adherence to the treatment.

Introduction: The importance of neurodegenerative diseases on the management of public health is growing and the real role of the environment and miRNA in their occurrence is still unclear. miRNA can significantly affect the regulatory network. The complex variety and gene-regulatory capacity of miRNAs are particularly valuable in the brain, being a very complex organ with a functional specialization of neurons highly adaptable to environmental stimuli. In particular, an miRNAs role is demonstrated in neurological diseases as an effect to toxic and mutagenic substances exposure by the environment. Objective: The focus was on the three most important neurodegenerative diseases: Alzheimer, Parkinson and Amyotrophic lateral sclerosis. Materials and Methods: A brief critical review on scientific papers of the last ten years using PuBMED, Scopus, Web of Science and Cochrane databases was carried out. Results: Several studies have shown that miRNAs may contribute to neurodegeneration process in response to environmental risks. The miRNAs are known to play a dynamic role in many biochemical pathways of mammalian's brain, including neuroplasticity, stress responses, cellular signaling, etc. miRNAs have a role in neurodegenerative phenotype of AD, PD and ALS. The environmental chemicals such as metals and pesticides and then behavior can cause miRNA alterations via increasing oxidative stress and/or triggering inflammatory responses. Conclusion: A discussion with theoretical and possible future research directions is provided and it is clear that the need is not only of longitudinal population studies and of better knowledge of epigenetics markers but, especially, of environmental policy interventions based on the green economy.

Aims: The many miRNAs discovered so far have been divided into biologically representative families, aiming at organizing and systematizing their study so to promote, mainly, a better understanding of their functionalities. Clustering miRNA sequences can corroborate the family-based organizations as well as helping to explore sequences belonging to the same cluster as potentially having similar biological functions. Observations: Considering that members of the same miRNA family tend to biologically function in similar ways, a well-structured family can help detecting miRNA functions which have not been associated yet with any existing family. Methods: The work described in this paper empirically investigates the suitability of organizing miRNAs as families, using a clustering algorithm based on a particular type of graph i.e., minimal spanning tree (MST), for clustering miRNA sequences. Seven miRNA families stored in the online miRBase database have been used as input to the MST-based clustering algorithm and clustering results have been compared to assess the suitability of identirying them. Results: The motivations for the experiments were to identify refinements in miRNA family organizations that could be pursued and, also, investigate how the chosen graph-based clustering algorithm would perform in miRNA related domains. Conclusion: Interesting and useful results, particularly related to detecting information based on the visualization of the final induced graphs, and their induced connected components (clusters), are presented and discussed. Particularly, experiments results suggested the possibility of refining some miRNA families by grouping some of their miRNAs as sub-families.

Background: Heptahelical G protein coupled receptors (GPCRs) support numerous sensory and metabolic functions and differ considerably in levels of expression. GPCR protein levels should link to regulation of GPCR mRNAs by microRNAs (miRs), which might significantly depend on numbers, size and GC content of the canonical antisense matches in mRNAs. These parameters of GPCR mRNAs have not been studied in detail. Methods: Canonical matching profiles of human GPCR mRNAs and miRs were examined using segments of 7-15 nucleotides in windows shifted by one position over the entire microRNA sequence. Results: Human GPCRs mRNAs within larger function-related groups have a quite homogenous matching with miRs. Both the GC content and the melting temperature (and hence also the binding energy) are appreciably higher in 5'utr compared to 3'utr matches of the same length. Increase in the GC content correlates significantly with length in the ubiquitous matches of 7-12 nucleotides. However, several GPCR groups strongly differ in overall match numbers and density. The untranslated regions of sensory receptor mRNAs, especially the olfactory and Taste-2 mRNAs, have the lowest match numbers and density and the fewest miR partners. The glucagon and frizzled families show the highest canonical matching. Conclusion: Partnership of GPCR mRNAs and miRs could significantly relate to the type of function of the receptor proteins, with mRNAs of the sensory receptors having the lowest and those of metabotropic GPCRs the highest targeting. This could be of interest regarding GPCR regulation by exogenous miRs.

History: Nuclear Hormone Receptors (NHRs) are the most important targets that play vital role in cellular signaling pathways of disease. Regulation of NHRs by using potential non-coding RNAs, miRNA, is clinically important to control a disease. However, the detailed status of miRNA interactions with NHRs remains unclear. Hence, the focus of the present study is to investigate the interface at the genome-wide level in human, mouse and rat using computational biology approach. Observations: This big-data analysis explored thousands of available miRNAs interactions with the NHRs and the results showed that 11 miRNAs have conserved targets, where six miRNAs are genetically conserved among different species. This implies that both conserved and non-conserved miRNAs have a potential role in NHRs regulation. We found several “Aberrantly Binding miRNAs” (ABMs) that can bind to the target NHR genes. In this study, for human miR-548, rat miR-Let-7 and miR-30, mouse miR-466 are identified as potential ABMs families. We also found the list of genes targeting ABMs. Results: Specifically, these miRNAs majorly targeted bind nuclear subfamily receptor genes in all studied animal species. ABMs family interaction with NHR genes is favored by AT richness and the length of the gene. Conclusion: Our findings suggest that, specific ABMs family targeting NHRs may act as potential candidates to regulate the downstream signaling pathways.

Background: MicroRNAs (miRNAs) are small, highly conserved non-coding RNA molecules involved in the RNA silencing and post-transcriptional regulation of gene expression. miRNAs are well conserved in both plants and animals, and are thought to be a vital and evolutionarily ancient component of gene regulation and also act as oncogenes or tumor suppressors. It is known that Express Sequence Tags (EST) are a short sub-sequence of cDNA sequence, which contain information of condition or tissue specific transcripts (coding and non-coding) of an organism. Methods: In the present study, we have applied the bioinformatics tools to identify miRNA from breast cancer using EST resource. Through bioinformatics approach, the presence of an EST encoding hsa-miR-17- 3p of breast cancer was identified. Results: Further studies reveal that hsa-miR-17 is confirmed in the breast cancer specific EST sequence among the predicted miRNAs secondary structure. Moreover, miR-17-3p could be responsible for a tumor suppression, which plays a major role in human breast cancer. Conclusion: Further studies are required to investigate the molecular mechanisms behind miR-17-3p involves in the suppression of breast cancer cells. Interestingly, our target analysis suggesting that all the targets involved in multiple signaling pathways in different cell regulations moreover, we need to have more number of in vitro and in vivo studies that prove miR-17-3p as candidate microRNA for breast cancer cells.

Background: Translational research on miRNAs develops reliable biomarkers for diagnosis and prognosis of renal diseases. Bioinformatic analyses and systems biology could drive the research for knowing new informative miRNA targets. Objectives: This study proposes an approach to identify miRNA specific significant target genes, and single nucleotide polymorphisms (SNPs) associated with renal pathophysiology. Methods: miRNAs were selected after removing duplicity, on the basis of techniques used, and disease spectrum width score. Target genes were predicted from different databases like miRWalk, miRTarBase, and DIANA-TarBase. SNPs were prioritized on the basis of target score and conserved energy score available in MirSNP database. miRNAs were characterized as “specific”, “strong”, “likely”, “unlikely”, and “irrelevant” biomarkers. PCR-SSP based genotyping was carried out to access the molecular profiling of hsa-miR-192 and TGF-β1 followed by quantitative real time PCR to analyze expression level of TGF-β1. The relative expression levels of mRNAs were analyzed by 2-ΔΔCt method. Results: 170 renal associated miRNAs were found to be up-regulated, down-regulated or differentially expressed. Noticeably hsa-miR-192-3p expression was reported in nine diseases. 117 genes were associated with basic kidney diseases and end stage renal disease (ESRD). Threshold > 80% for 93 target genes was observed from mirSVR. Mutant genotypes for hsa-miR-192 (OR=4.64, p-value ≤ 0.0001) and its corresponding target gene TGF-β1 (OR = 0.70, p-value = 0.0351) showed susceptible association with ESRD. More so, patients possessing mutant allele of TGF-β1 showed elevated mRNA expression (Fold change = 9.83). Conclusion: Study proposed a new approach to identify specific miRNA biomarkers for particular diseases with corresponding target genes and SNPs and also highlighted the importance of hsa-miR- 192 in renal diseases.