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Serum response factor (SRF) cooperates with various co-factors to manage the specification of diverse cell lineages during heart development. Many microRNAs mediate the function of SRF in this process. However, how are miR210 and miR30c involved in the decision of cardiac cell fates remains to be explored. In this study, we found that SRF directly controlled the cardiac expression of miR210. Both miR210 and miR30c blocked the formation of beating cardiomyocyte during embryoid body (EB) differentiation, a cellular model widely used for studying cardiogenesis. Both of anticipated microRNA targets and differentially expressed genes in day8 EBs were systematically determined and enriched with gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) and Reactome. Functional enrichments of prediction microRNA targets and down-regulated genes in day8 EBs of miR210 suggested the importance of PI3K-Akt signal and ETS2 in miR210 inhibition of cardiomyocyte differentiation. Similar analyses revealed that miR30c repressed both developmental progress and the adrenergic signaling in cardiomyocytes during the differentiation of EBs. Taken together, SRF directs the expression of miR210 and miR30c, and they repress cardiac development via inhibiting the differentiation of cardiac muscle cell lineage as well as the cell proliferation. Through the regulation of specific microRNAs, the complication of SRF's function in heart development is emphasized. • Both miR210 and miR30c blocked the formation of beating cardiomyocyte in the embryoid body differentiation system. • Functional enrichments of potentially direct targets of either microRNA indicated their inhibition of development, PI3K-Akt signaling or the adrenergic signaling. [ABSTRACT FROM AUTHOR]

The limb-bud and heart development (LBH) gene is a highly conserved, tissue-specific transcription cofactor in vertebrates that regulates multiple key genes in embryonic development. The role of LBH in various cancer types is still controversial, and its specific role and molecular mechanism in the oncogenesis of gastric cancer (GC) remains largely unexplored. In the present study, the prognostic significance and clinicopathological characteristics of LBH in GC was determined. The LBH mRNA expression was first investigated in four independent public datasets (TCGA-STAD, GSE15459, GSE29272, and GSE62254) and then validated with our samples at the protein level. LBH was overexpressed at both the mRNA and protein levels in cancer compared with normal tissues. High LBH expression was correlated with advanced T, N, and M stages. Kaplan–Meier analysis and log-rank test indicated that higher LBH expression was statistically correlated with shorter overall survival (OS) in the public datasets and our study samples. Univariate and multivariate Cox regression analysis showed that LBH was an independent prognostic biomarker for survival in TCGA-STAD, GSE15459, GSE62254 cohorts, and our GC patients. In vitro experiments showed that knockdown of LBH can significantly inhibit the proliferation and invasion of HGC-27 cells, while overexpression of LBH can significantly enhance the proliferation and invasion of BGC-823 cells. Gene Set Enrichment Analysis (GSEA), Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG) indicated that high LBH expression is associated with the PI3K-Akt pathway, focal adhesion, and extracellular matrix (ECM)-receptor interaction. Western blot analysis showed that knockdown of LBH significantly inhibited the expression of integrin α5, integrin β1, p-FAK, and p-Akt. Therefore, results from the present study indicate that LBH is a potential independent prognostic biomarker and promotes proliferation and invasion of GC cells by activating the integrin/FAK/Akt pathway. [ABSTRACT FROM AUTHOR]

We studied the effect of hypokinesia combined with cold exposure on morphological parameters of the heart in Wistar-Kyoto rats and rats with spontaneous genetically determined hypertension (SHR). The pathological processes developing in the heart of white laboratory rats significantly affected cardiac function and manifested in the deterioration of the morphological structure of the heart: reduction of heart weight, thinning of the free wall of the left ventricle. These changes indicate transition to a lower energy level of functioning. At the same time, hypertrophy of the right free wall develops in both rat lines. Combined effect of hypokinesia and cold is probably a factor indirectly promoting the development of pulmonary heart. [ABSTRACT FROM AUTHOR]