Analysis of the function of microRNA-375 in humans using bioinformatics

Abstract

Abstract. ) is expressed at low levels in many types of solid tumor, particularly in gastrointestinal tumors. It is considered to be important in the development of cancer and certain diseases. Thus, more detailed knowledge is required on the particular functions of miR-375. miRs function by regulating target genes. Therefore, in the current study, miRWalk (which includes the data from 10 prediction software programs) was used to predict the target genes of miR-375. The genes, which were co-predicted using five different software programs were further analyzed using Database for Annotation, Visualization and Integrated Discovery online software [including gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis]. Subsequently, the online tool, Search Tool for the Retrieval of Interacting Genes, was used to analyze the protein-protein interaction and construct modules using Cytoscape. The result demonstrated 6,574 predicted genes, 1,325 of which were co-predicted. The GO analysis result indicated that, in biological processes, the co-predicted genes were significantly enriched in the regulation of nervous system development and cell differentiation, and the highest enrichment of molecular function was ion binding. In KEGG analysis, the genes were enriched in the Hippo signaling pathway, glutamatergic synapse, circadian entrainment and the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway. The top 10 hub proteins were mechanistic target of rapamycin, PH domain and leucine rich repeat protein phosphatase 1, ubiquitously transcribed tetratricopeptide repeat containing, Y-linked, histone deacetylase 2, F-box and leucine rich repeat protein 19, KIT proto-oncogene receptor tyrosine kinase, angiotensinogen, Janus kinase 2, fibroblast growth factor 2 and RNA polymerase II subunit A. These proteins predominantly regulate the development and progression of cancer, hypertension, essential thrombocythemia and inflammation. The genes in the top seven modules selected were identified to be primarily enriched in chemokines, extracellular matrix-receptor interaction, focal adhesion, the PI3K-Akt signaling pathway, amoebiasis and protein processing signaling pathway. Thus, the target genes and hub proteins that were predicted in the current study were identified to be important in regulating the development and progression of cancer and certain diseases. Furthermore, they present potential novel biomarkers for tumor diagnosis and candidate targets for treatment, and indicate that further research is required to establish the functions of miR-375.

Intermittent Hypoxia Increased the Expression of DBH and PNMT in Neuroblastoma Cells via MicroRNA-375-Mediated Mechanism

“…Several miRs with altered expression in catecholamine-producing pheochromocytomas and paragangliomas (such as miR-15, -16, -21-3p, -96, -101-, -133, -137, -139-3p, -183, -195, -210, -338-3p, -375, -382, -483-5p, -488, -508, -765, -855, and -1225-3p) were reported [ 35 ]. In particular, there are a few reports on the function of miR-375, and they suggested it to be involved in the regulation of cytokines, extracellular matrix–receptor interaction, focal adhesion, phosphatidylinositol-3 kinase-protein kinase B (Akt), amoebiasis, and protein-processing pathways [ 36 ]. Single nucleotide polymorphisms (rs11174811 and rs3803107) in miR-375 target sites of the 3′-untranslated region in the arginine vasopressin receptor 1a gene were reported to be associated with the risk of hypertension [ 37 ].…”

Predictive role of plasmatic biomarkers in advanced non-small cell lung cancer treated by nivolumab

“…44,48,51,54,[56][57][58][59] In NSCLC, miRNA-375 is associated with poor prognosis. 43,44,60 Interestingly, miRNA-375 is strongly associated with the Wnt/ b-catenine pathway 49 and the Hippo pathway, 59,[61][62][63] known to be involved in ICIs resistance. [64][65][66][67][68][69][70] Moreover, miRNA-375 targets the JAK2 gene, 62,71 involved in the IFN-g and TNF-a pathways, key-regulators of cytotoxic CD8C immune response.…”

“…43,44,60 Interestingly, miRNA-375 is strongly associated with the Wnt/ b-catenine pathway 49 and the Hippo pathway, 59,[61][62][63] known to be involved in ICIs resistance. [64][65][66][67][68][69][70] Moreover, miRNA-375 targets the JAK2 gene, 62,71 involved in the IFN-g and TNF-a pathways, key-regulators of cytotoxic CD8C immune response. 72 Taken together, these data, highlighted by our results, suggest an implication of both miRNA-320b and miRNA-375 in anti-tumour immune response with ICIs, and the potential utility of screening for these miRNA in plasma before beginning nivolumab to select patients who will have response and clinical benefit with this treatment.…”

Hsa-miR-34a-5p and hsa-miR-375 as Biomarkers for Monitoring the Effects of Drug Treatment for Migraine Pain in Children and Adolescents: A Pilot Study

“…Moreover, in a clinical study, Andersen and colleagues [25] described an increased expression of has-miR-34a-5p in patients with migraine attacks, while Chen et al [26] reported that hsa-miR-375 plays pivotal roles in cancer, metabolic, immune disease and inflammatory diseases.…”