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LncRNA DCRF regulates cardiomyocyte autophagy by targeting miR-551b-5p in diabetic cardiomyopathy

Background: We generated a rat model of diabetic cardiomyopathy (DCM) and reported significant upregulation of the long non-coding RNA DCRF. This study was designed to determine the molecular mechanisms of DCRF in the development of DCM. Methods: Real-time PCR and RNA fluorescent in situ hybridizati...

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Autores principales: Feng, Yu, Xu, Weiting, Zhang, Wei, Wang, Wenjing, Liu, Tong, Zhou, Xiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599651/
https://www.ncbi.nlm.nih.gov/pubmed/31285779
http://dx.doi.org/10.7150/thno.31052
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author Feng, Yu
Xu, Weiting
Zhang, Wei
Wang, Wenjing
Liu, Tong
Zhou, Xiang
author_facet Feng, Yu
Xu, Weiting
Zhang, Wei
Wang, Wenjing
Liu, Tong
Zhou, Xiang
author_sort Feng, Yu
collection PubMed
description Background: We generated a rat model of diabetic cardiomyopathy (DCM) and reported significant upregulation of the long non-coding RNA DCRF. This study was designed to determine the molecular mechanisms of DCRF in the development of DCM. Methods: Real-time PCR and RNA fluorescent in situ hybridization were conducted to detect the expression pattern of DCRF in cardiomyocytes. Histological and echocardiographic analyses were used to assess the effect of DCRF knockdown on cardiac structure and function in diabetic rats. mRFP-GFP-LC3 fluorescence microscopy, transmission electron microscopy, and Western blotting were carried out to determine cardiomyocyte autophagy. RNA immunoprecipitation and luciferase reporter assays were performed to elucidate the regulatory role of DCRF/miR-551b-5p/PCDH17 pathway in cardiomyocyte autophagy. Results: Our findings showed that DCRF knockdown reduced cardiomyocyte autophagy, attenuated myocardial fibrosis, and improved cardiac function in diabetic rats. High glucose increased DCRF expression and induced autophagy in cardiomyocytes. RNA immunoprecipitation and luciferase reporter assays indicated that DCRF was targeted by miR-551b-5p in an AGO2-dependent manner and PCDH17 was the direct target of miR-551b-5p. Forced expression of DCRF was found to attenuate the inhibitory effect of miR-551b-5p on PCDH17. Furthermore, DCRF knockdown decreased PCDH17 expression and suppressed autophagy in cardiomyocytes treated with high glucose. Conclusion: Our study suggests that DCRF can act as a competing endogenous RNA to increase PCDH17 expression by sponging miR-551b-5p, thus contributing to increased cardiomyocyte autophagy in DCM.
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spelling pubmed-65996512019-07-08 LncRNA DCRF regulates cardiomyocyte autophagy by targeting miR-551b-5p in diabetic cardiomyopathy Feng, Yu Xu, Weiting Zhang, Wei Wang, Wenjing Liu, Tong Zhou, Xiang Theranostics Research Paper Background: We generated a rat model of diabetic cardiomyopathy (DCM) and reported significant upregulation of the long non-coding RNA DCRF. This study was designed to determine the molecular mechanisms of DCRF in the development of DCM. Methods: Real-time PCR and RNA fluorescent in situ hybridization were conducted to detect the expression pattern of DCRF in cardiomyocytes. Histological and echocardiographic analyses were used to assess the effect of DCRF knockdown on cardiac structure and function in diabetic rats. mRFP-GFP-LC3 fluorescence microscopy, transmission electron microscopy, and Western blotting were carried out to determine cardiomyocyte autophagy. RNA immunoprecipitation and luciferase reporter assays were performed to elucidate the regulatory role of DCRF/miR-551b-5p/PCDH17 pathway in cardiomyocyte autophagy. Results: Our findings showed that DCRF knockdown reduced cardiomyocyte autophagy, attenuated myocardial fibrosis, and improved cardiac function in diabetic rats. High glucose increased DCRF expression and induced autophagy in cardiomyocytes. RNA immunoprecipitation and luciferase reporter assays indicated that DCRF was targeted by miR-551b-5p in an AGO2-dependent manner and PCDH17 was the direct target of miR-551b-5p. Forced expression of DCRF was found to attenuate the inhibitory effect of miR-551b-5p on PCDH17. Furthermore, DCRF knockdown decreased PCDH17 expression and suppressed autophagy in cardiomyocytes treated with high glucose. Conclusion: Our study suggests that DCRF can act as a competing endogenous RNA to increase PCDH17 expression by sponging miR-551b-5p, thus contributing to increased cardiomyocyte autophagy in DCM. Ivyspring International Publisher 2019-06-10 /pmc/articles/PMC6599651/ /pubmed/31285779 http://dx.doi.org/10.7150/thno.31052 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Feng, Yu
Xu, Weiting
Zhang, Wei
Wang, Wenjing
Liu, Tong
Zhou, Xiang
LncRNA DCRF regulates cardiomyocyte autophagy by targeting miR-551b-5p in diabetic cardiomyopathy
title LncRNA DCRF regulates cardiomyocyte autophagy by targeting miR-551b-5p in diabetic cardiomyopathy
title_full LncRNA DCRF regulates cardiomyocyte autophagy by targeting miR-551b-5p in diabetic cardiomyopathy
title_fullStr LncRNA DCRF regulates cardiomyocyte autophagy by targeting miR-551b-5p in diabetic cardiomyopathy
title_full_unstemmed LncRNA DCRF regulates cardiomyocyte autophagy by targeting miR-551b-5p in diabetic cardiomyopathy
title_short LncRNA DCRF regulates cardiomyocyte autophagy by targeting miR-551b-5p in diabetic cardiomyopathy
title_sort lncrna dcrf regulates cardiomyocyte autophagy by targeting mir-551b-5p in diabetic cardiomyopathy
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599651/
https://www.ncbi.nlm.nih.gov/pubmed/31285779
http://dx.doi.org/10.7150/thno.31052
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