MiR-1-3p that correlates with left ventricular function of HCM can serve as a potential target and differentiate HCM from DCM
Abstract Background MicroRNAs (miRNAs) are non-coding RNAs that function as regulators of gene expression and thereby contribute to the complex disease phenotypes. Hypertrophic cardiomyopathy (HCM) and Dilated cardiomyopathy (DCM) can cause sudden cardiac death and eventually develop into heart fail...
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doaj-b524bd507241471ebcc96f49dd3ad2da2020-11-25T02:08:39ZengBMCJournal of Translational Medicine1479-58762018-06-0116111010.1186/s12967-018-1534-3MiR-1-3p that correlates with left ventricular function of HCM can serve as a potential target and differentiate HCM from DCMMengmeng Li0Xiao Chen1Liang Chen2Kai Chen3Jianye Zhou4Jiangping Song5State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract Background MicroRNAs (miRNAs) are non-coding RNAs that function as regulators of gene expression and thereby contribute to the complex disease phenotypes. Hypertrophic cardiomyopathy (HCM) and Dilated cardiomyopathy (DCM) can cause sudden cardiac death and eventually develop into heart failure. However, they have different clinical and pathophysiological phenotype and the expressional spectrum of miRNAs in left ventricles of HCM and DCM has never been compared before. Methods This study selected 30 human left ventricular heart samples belonged to three diagnostic groups (Control, HCM, DCM). Each group has ten samples. Based on previous findings, the expression of 13 different microRNAs involving heart failure and hypertrophy (miR-1-3p, miR-10b, miR-21, miR-23a, miR-27a, miR-29a, miR-133a-3p, miR-142-3p, miR-155, miR-199a-3p, miR-199a-5p, miR-214, miR-497) was measured. 17 HCM patients were included as second group to validate the associations. Results We found miR-155, miR-10b and miR-23a were highly expressed in both HCM and DCM compared with control. MiR-214 was downregulated and miR-21 was upregulated in DCM but not in HCM. We also identified miR-1-3p and miR-27a expressed significantly different between HCM and DCM and both miRNAs downregulated in HCM. And only miR-1-3p correlated with left ventricular end diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) that reflected the cardiac function in HCM. A second HCM group also confirmed this correlation. We then predicted Chloride voltage-gated channel 3 (Clcn3) as a direct target gene of miR-1-3p using bioinformatics tools and confirmed it by Luciferase reporter assay. Conclusion Our data demonstrated that different cardiomyopathies had unique miRNA expression pattern. And the expression levels of miR-1-3p and miR-27a had disease-specificity and sensitivity in HCM, whereas only miR-1-3p was significantly associated with left ventricular function in HCM identifying it as a potential target to improve the cardiac function in end-stage HCM. We also provide Clcn3 as a direct target of miR-1-3p which sheds light on the mechanism of HCM.http://link.springer.com/article/10.1186/s12967-018-1534-3HCMDCMmicroRNALeft ventricular functionClcn3 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mengmeng Li Xiao Chen Liang Chen Kai Chen Jianye Zhou Jiangping Song |
spellingShingle |
Mengmeng Li Xiao Chen Liang Chen Kai Chen Jianye Zhou Jiangping Song MiR-1-3p that correlates with left ventricular function of HCM can serve as a potential target and differentiate HCM from DCM Journal of Translational Medicine HCM DCM microRNA Left ventricular function Clcn3 |
author_facet |
Mengmeng Li Xiao Chen Liang Chen Kai Chen Jianye Zhou Jiangping Song |
author_sort |
Mengmeng Li |
title |
MiR-1-3p that correlates with left ventricular function of HCM can serve as a potential target and differentiate HCM from DCM |
title_short |
MiR-1-3p that correlates with left ventricular function of HCM can serve as a potential target and differentiate HCM from DCM |
title_full |
MiR-1-3p that correlates with left ventricular function of HCM can serve as a potential target and differentiate HCM from DCM |
title_fullStr |
MiR-1-3p that correlates with left ventricular function of HCM can serve as a potential target and differentiate HCM from DCM |
title_full_unstemmed |
MiR-1-3p that correlates with left ventricular function of HCM can serve as a potential target and differentiate HCM from DCM |
title_sort |
mir-1-3p that correlates with left ventricular function of hcm can serve as a potential target and differentiate hcm from dcm |
publisher |
BMC |
series |
Journal of Translational Medicine |
issn |
1479-5876 |
publishDate |
2018-06-01 |
description |
Abstract Background MicroRNAs (miRNAs) are non-coding RNAs that function as regulators of gene expression and thereby contribute to the complex disease phenotypes. Hypertrophic cardiomyopathy (HCM) and Dilated cardiomyopathy (DCM) can cause sudden cardiac death and eventually develop into heart failure. However, they have different clinical and pathophysiological phenotype and the expressional spectrum of miRNAs in left ventricles of HCM and DCM has never been compared before. Methods This study selected 30 human left ventricular heart samples belonged to three diagnostic groups (Control, HCM, DCM). Each group has ten samples. Based on previous findings, the expression of 13 different microRNAs involving heart failure and hypertrophy (miR-1-3p, miR-10b, miR-21, miR-23a, miR-27a, miR-29a, miR-133a-3p, miR-142-3p, miR-155, miR-199a-3p, miR-199a-5p, miR-214, miR-497) was measured. 17 HCM patients were included as second group to validate the associations. Results We found miR-155, miR-10b and miR-23a were highly expressed in both HCM and DCM compared with control. MiR-214 was downregulated and miR-21 was upregulated in DCM but not in HCM. We also identified miR-1-3p and miR-27a expressed significantly different between HCM and DCM and both miRNAs downregulated in HCM. And only miR-1-3p correlated with left ventricular end diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) that reflected the cardiac function in HCM. A second HCM group also confirmed this correlation. We then predicted Chloride voltage-gated channel 3 (Clcn3) as a direct target gene of miR-1-3p using bioinformatics tools and confirmed it by Luciferase reporter assay. Conclusion Our data demonstrated that different cardiomyopathies had unique miRNA expression pattern. And the expression levels of miR-1-3p and miR-27a had disease-specificity and sensitivity in HCM, whereas only miR-1-3p was significantly associated with left ventricular function in HCM identifying it as a potential target to improve the cardiac function in end-stage HCM. We also provide Clcn3 as a direct target of miR-1-3p which sheds light on the mechanism of HCM. |
topic |
HCM DCM microRNA Left ventricular function Clcn3 |
url |
http://link.springer.com/article/10.1186/s12967-018-1534-3 |
work_keys_str_mv |
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