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• W2569240815 abstract "Heart failure (HF) is a widely prevalent syndrome imposing a significant burden of morbidity and mortality world-wide. Differential circulating microRNA profiles observed in HF cohorts suggest the diagnostic utility of microRNAs as biomarkers. Given their function in fine tuning gene expression, alternations in microRNA landscape could reflecting the underlying mechanisms of disease and present potential therapeutic targets. Using multiple computational target predicting algorithms together with the luciferase-based reporting platform, the interactions between HF-related microRNAs and the 3′ untranslated regions (3′UTRs) of neurohormone associated genes were examined and compared. Our results indicate that although in silico prediction provides an overview of possible microRNA-mRNA target pairs, less than half of the predicted interactions were experimentally confirmed by reporter assays in HeLa cells. Thus, the establishment of microRNA/3′UTR reporters is essential to systemically evaluate the roles of microRNAs for signaling cascades of interest, including cardiovascular neurohormonal signaling. The physiological relevance of HF-related microRNAs on the expression of putative gene targets was further established by using gain-of-function assays in two human cardiac-derived cells. Our findings, for the first time, provide direct evidence of the regulatory effects of HF-related microRNAs on the neurohormonal signaling in cardiac cells. More importantly, our study presents a rational approach to further exploring microRNA profiling data in deciphering the role of microRNA in complex syndromes such as HF. This article is part of a Special Issue entitled: Genetic and epigenetic control of heart failure - edited by Jun Ren & Megan Yingmei Zhang. • Heart failure-related microRNAs regulate the expression of neurohormone-associated genes. • 318 neurohormone-associated gene targets were computationally predicted to be targeted by HF related microRNAs. • Significant discrepancies between predicted and experimentally validated gene targets were observed. • A panel of 30 3′UTR luciferase reporter constructs was built for microRNA-target interaction screening. • HF-related microRNAs regulate neurohormonal signaling in human cardiac-derived cells." @default.
• W2569240815 created "2017-01-13" @default.
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• W2569240815 date "2017-08-01" @default.
• W2569240815 modified "2023-09-25" @default.
• W2569240815 title "The association of heart failure-related microRNAs with neurohormonal signaling" @default.
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• W2569240815 doi "https://doi.org/10.1016/j.bbadis.2016.12.019" @default.
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