title: The association of heart failure-related microRNAs with neurohormonal signaling.
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.
authors.affiliation: Cardiovascular Research Institute, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, #08-01, MD6 Centre for Translational Medicine, 14 Medical Drive, 117599, Singapore. Electronic address: mdccyt@nus.edu.sg.
authors.forename: Yei-Tsung
authors.initials: YT
authors.lastname: Chen
authors.affiliation: Cardiovascular Research Institute, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, #08-01, MD6 Centre for Translational Medicine, 14 Medical Drive, 117599, Singapore. Electronic address: mdcwaju@nus.edu.sg.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Cardiovascular Research Institute, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, #08-01, MD6 Centre for Translational Medicine, 14 Medical Drive, 117599, Singapore. Electronic address: mdctks@nus.edu.sg.
authors.forename: Kai Sing
authors.initials: KS
authors.lastname: Tong
authors.affiliation: Cardiovascular Research Institute, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, #08-01, MD6 Centre for Translational Medicine, 14 Medical Drive, 117599, Singapore. Electronic address: mdcwll@nus.edu.sg.
authors.forename: Lee Lee
authors.initials: LL
authors.lastname: Wong
authors.affiliation: Cardiovascular Research Institute, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, #08-01, MD6 Centre for Translational Medicine, 14 Medical Drive, 117599, Singapore. Electronic address: mdclow@nus.edu.sg.
authors.forename: Oi Wah
authors.initials: OW
authors.lastname: Liew
authors.affiliation: Cardiovascular Research Institute, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, #08-01, MD6 Centre for Translational Medicine, 14 Medical Drive, 117599, Singapore; Cardiac Department, National University Health System, Tower Block Level 9, 1E Kent Ridge Road, 119228, Singapore; Christchurch Heart Institute, Department of Medicine, University of Otago, PO Box 4345, Christchurch 8014, New Zealand. Electronic address: arthur_mark_richards@nuhs.edu.sg.
authors.forename: Arthur Mark
authors.initials: AM
authors.lastname: Richards
mesh_terms: D020413:3' Untranslated Regions; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs
keywords: Heart failure; MicroRNA; Neurohormone