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Background and objectives The control of cardiomyocyte differentiation is tightly linked to micro RNAs (mi RNAs), which have been emerging as important players in heart development. However, the regulation mechanisms mediated by mi RNAs in early heart development remains speculative. Here, we evaluated the impact of miR-26b during the progression of cardiomyocyte differentiation from the P19 cell line. Materials and methods The overexpression of miR-26b in P19 cells was performed by transduction with lentivirus vector. The levels of cardiac-related genes during P19 cell differentiation were detected using quantitative real-time PCR for mRNA abundance and Western blots for protein expression. ICG-001 was applied to elucidate the role of β-catenin on P19 cells differentiation. The Cell Counting kit-8 ( CCK-8) was used to monitor the cell proliferation. The target genes of miR-26b were validated using the dual luciferase reporter system. Results Overexpression of miR-26b upregulates the expression level of cardiomyocyte-related genes such as Gata4, cTNT, α- MHC and α-Actinin that comprehensively represent cardiomyocyte differentiation by effecting Wnt5a signalling and Gsk3β activity. However, ICG-001 blocks the differentiation along with inhibition of the cell proliferation. In addition, miR-26b also regulates CyclinD1 to promote P19 cell proliferation, thereby, demonstrating the rapid aggregation and differentiation programming of these cells into cardiomyocytic types. Conclusions Our results indicated that miR-26b exerts a role on promoting cardiomyocyte differentiation of P19 cells by controlling the canonical and non-canonical Wnt signalling. [ABSTRACT FROM AUTHOR]

microRNAs (miRNAs) play essential roles in cardiogenesis. The altered expression of miRNAs can result in cardiac malformations by inducing abnormalities in the behavior of cardiac cells. However, the role of miR-10a in the regulation of cardiomyocyte progenitor cells (CMPCs) remains undetermined. In the present study, we found that up- or down-regulation of miR-10a inhibited or promoted the proliferation of human CMPCs, respectively, without affecting their differentiation toward cardiomyocytes. miR-10a bound to GATA6 directly and reduced GATA6 expression. Over-expression of GATA6 greatly attenuated the miR-10a-mediated inhibitory effect on the proliferation of human CMPCs. Thus, our results indicate that miR-10a could effectively modulate the proliferation of human CMPCs by targeting GATA6. The finding provides novel insights into the potency of miR-10a during heart development. [ABSTRACT FROM AUTHOR]

It has become increasingly clear that the current taxonomy of clinical phenotypes is mixed with molecular heterogeneity, which potentially affects the treatment effect for involved patients. Defining the hidden molecular-distinct diseases using modern large-scale genomic approaches is therefore useful for refining clinical practice and improving intervention strategies. Given that microRNA expression profiling has provided a powerful way to dissect hidden genetic heterogeneity for complex diseases, the aim of the study was to develop a bioinformatics approach that identifies microRNA features leading to the hidden subtyping of complex clinical phenotypes. The basic strategy of the proposed method was to identify optimal miRNA clusters by iteratively partitioning the sample and feature space using the two-ways super-paramagnetic clustering technique. We evaluated the obtained optimal miRNA cluster by determining the consistency of co-expression and the chromosome location among the within-cluster microRNAs, and concluded that the optimal miRNA cluster could lead to a natural partition of disease samples. We applied the proposed method to a publicly available microarray dataset of breast cancer patients that have notoriously heterogeneous phenotypes. We obtained a feature subset of 13 microRNAs that could classify the 71 breast cancer patients into five subtypes with significantly different five-year overall survival rates (45%, 82.4%, 70.6%, 100% and 60% respectively; p = 0.008). By building a multivariate Cox proportional-hazards prediction model for the feature subset, we identified has-miR-146b as one of the most significant predictor (p = 0.045; hazard ratios = 0.39). The proposed algorithm is a promising computational strategy for dissecting hidden genetic heterogeneity for complex diseases, and will be of value for improving cancer diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Cardiac dysfunction represents a main component of death induced by sepsis in critical care units. And microRNAs (miRNAs) have been reported as important modulators or biomarkers of sepsis. However, the molecular detail of miRNAs involved in septic cardiac dysfunction remains unclear. Here we showed that endotoxin (lipopolysaccharide, LPS) significantly down-regulated expression of miR-29b-3p in heart. Increased expression of miR-29b-3p by lentivirus improved cardiac function and attenuated damage of cardiac induced by LPS in mice. Furthermore, overexpression or knockdown of miR-29b-3p showed its crucial roles on regulation of apoptosis and production of pro-inflammatory cytokines in NRCMs through directly targeting FOXO3A. miR-29b-3p ameliorates inflammatory damage likely via reducing activation of MAPKs and nuclear-translocation of NF-κB to block LPS-activated NF-κB signaling. Notably, miR-29b is also down-regulated in septic patients' plasma compared with normal subjects, indicating a potential clinical relevance of miR-29b. Taken together, our findings demonstrate that upregulation of miR-29b-3p can attenuate myocardial injury induced by sepsis via regulating FOXO3A, which provide a potential therapy target for interference of septic cardiac dysfunction. Unlabelled Image • Downregulation of miR-29b-3p in plasma of septic patients and LPS-treated heart. • miR-29b-3p attenuates cardiomyocytes apoptosis and inflammatory response. • FOXO3A was identified as a target gene of miR-29b-3p and mediated its effects. • MAPKs/NF-kB signaling pathway involved in regulation of miR-29b-3p/FOXO3A. [ABSTRACT FROM AUTHOR]