Implication of miR-612 and miR-1976 in the regulation of TP53 and CD40 and their relationship in the response to specific weight-loss diets

Abstract

BackgroundNon-coding RNAs (i.e., miRNAs) play a role in the development of obesity and related comorbidities and the regulation of body weight.ObjectiveTo identify candidate miRNA biomarkers throughout omics approaches in order to predict the response to specific weight-loss dietary treatments.DesignGenomic DNA and cDNA isolated from white blood cells of a subset from the RESMENA nutritional intervention study (Low-responders (LR) vs High-responders (HR)) was hybridized in Infinium Human Methylation450 BeadChip and in Illumina Human HT-12 v4 gene expression BeadChips arrays respectively. A bioinformatic prediction of putative target sites of selected miRNAs was performed by applying miRBase algorithms. HEK-293T cells were co-transfected with expression vectors containing the 3’-UTR of candidate genes to validate the binding of miRNAs to its target sites.Results134 miRNAs were differentially methylated between HR and LR in the methylation array, whereas 44 miRNAs were differentially expressed between both groups in the expression array. Specifically, miR-1237, miR-1976, miR-642, miR-636, miR-612 and miR-193B were simultaneously hypomethylated and overexpressed in HR. miR-612 and miR-1976 showed greatest differences in methylation and expression levels, respectively. The bioinformatic prediction revealed that TP53 was a putative target gene of miR-612 and CD40 of miR-1976. Moreover, TP53 was downregulated in the expression array when comparing HR vs LR expression levels adjusted by sex, diet, age and baseline weight, and CD40 showed a statistical trend. Furthermore, gene expression levels of TP53 and CD40 in white blood cells, when measured by qPCR, were also downregulated in HR. Finally, miR-612 and miR-1976 potently repressed TP53 and CD40 respectively by targeting its 3’-UTR regions.ConclusionmiR-612 and miR-1976 levels could be prospective biomarkers of response to specific weight-loss diets and might regulate the gene expression of TP53 and CD40.

MiR‐16, as a potential NF‐κB‐related miRNA, exerts anti‐inflammatory effects on LPS‐induced myocarditis via mediating CD40 expression: A preliminary study

“…Bo et al have stated that CD40‐Ig intervention could mitigate myocardial injury. Moreover, a growing number of articles have discovered that CD40 is closely modulated by many miRNAs via directly targeting its 3′‐UTR . According to miRNA profiling, the overexpression of several miRNAs in the progression of atherosclerosis was reduced after CD40 ablation .…”

Gene Expression Profiling of MicroRNAs in HPV-Induced Warts and Normal Skin

“…In hepatocellular carcinoma patients, miR-612 inhibits the metastasis and epithelial-mesenchymal transition of cancer cells by targeting the AKT2 gene [57]. In addition, this miRNA has been reported as a potential regulator of TP53 and CD40 expression in adults with metabolic syndrome [58]. As can be seen, it appears that miR-612 possess antitumor functions in malignant lesions, which might explain why it was found to be downregulated in benign lesions such as warts.…”

miR-1185-1 and miR-548q Are Biomarkers of Response to Weight Loss and Regulate the Expression of GSK3B

“…As no differences were found either in anthropometric or in biochemical variables between groups after the intervention, both dietary groups were merged to increase the statistical power of the study. After the dietary intervention, aiming to identify miRNA-type biomarkers implicated in the response to the weight-loss intervention, participants were categorized into "high responders" (HR), when weight loss was ≥8%, and "low responders" (LR) when weight loss was ≤8%, as previously published [21]. After categorization, samples from both groups were randomly selected and were adjusted for sex, gender and weight prior to microarray analysis.…”

“…For example, circulating miR-935 and miR-140 levels were described as biomarkers of the magnitude of weight loss in an exercise and nutritional intervention [19]. Moreover, our group has previously demonstrated that miRNAs expression in blood cells could be also used as a prognostic biomarker of weight loss [20,21]. In this study, we aimed to search for miRNA-type biomarkers capable of predicting the response to a specific dietary treatment, in an attempt to elucidate their impact on the expression of target genes and their mechanism of action.…”