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Long non-coding RNA KCND1 protects hearts from hypertrophy by targeting YBX1

Cardiac hypertrophy is a common structural remodeling in many cardiovascular diseases. Recently, long non-coding RNAs (LncRNAs) were found to be involved in the physiological and pathological processes of cardiac hypertrophy. In this study, we found that LncRNA KCND1 (LncKCND1) was downregulated in...

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Autores principales: Yang, Rui, Li, Liangliang, Hou, Yumeng, Li, Yingnan, Zhang, Jing, Yang, Na, Zhang, Yuhan, Ji, Weihang, Yu, Tong, Lv, Lifang, Liang, Haihai, Li, Xuelian, Li, Tianyu, Shan, Hongli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10229629/
https://www.ncbi.nlm.nih.gov/pubmed/37253771
http://dx.doi.org/10.1038/s41419-023-05852-7
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author Yang, Rui
Li, Liangliang
Hou, Yumeng
Li, Yingnan
Zhang, Jing
Yang, Na
Zhang, Yuhan
Ji, Weihang
Yu, Tong
Lv, Lifang
Liang, Haihai
Li, Xuelian
Li, Tianyu
Shan, Hongli
author_facet Yang, Rui
Li, Liangliang
Hou, Yumeng
Li, Yingnan
Zhang, Jing
Yang, Na
Zhang, Yuhan
Ji, Weihang
Yu, Tong
Lv, Lifang
Liang, Haihai
Li, Xuelian
Li, Tianyu
Shan, Hongli
author_sort Yang, Rui
collection PubMed
description Cardiac hypertrophy is a common structural remodeling in many cardiovascular diseases. Recently, long non-coding RNAs (LncRNAs) were found to be involved in the physiological and pathological processes of cardiac hypertrophy. In this study, we found that LncRNA KCND1 (LncKCND1) was downregulated in both transverse aortic constriction (TAC)-induced hypertrophic mouse hearts and Angiotensin II (Ang II)-induced neonatal mouse cardiomyocytes. Further analyses showed that the knockdown of LncKCND1 impaired cardiac mitochondrial function and led to hypertrophic changes in cardiomyocytes. In contrast, overexpression of LncKCND1 inhibited Ang II-induced cardiomyocyte hypertrophic changes. Importantly, enhanced expression of LncKCND1 protected the heart from TAC-induced pathological cardiac hypertrophy and improved heart function in TAC mice. Subsequent analyses involving mass spectrometry and RNA immunoprecipitation assays showed that LncKCND1 directly binds to YBX1. Furthermore, overexpression of LncKCND1 upregulated the expression level of YBX1, while silencing LncKCND1 had the opposite effect. Furthermore, YBX1 was downregulated during cardiac hypertrophy, whereas overexpression of YBX1 inhibited Ang II-induced cardiomyocyte hypertrophy. Moreover, silencing YBX1 reversed the effect of LncKCND1 on cardiomyocyte mitochondrial function and its protective role in cardiac hypertrophy, suggesting that YBX1 is a downstream target of LncKCND1 in regulating cardiac hypertrophy. In conclusion, our study provides mechanistic insights into the functioning of LncKCND1 and supports LncKCND1 as a potential therapeutic target for pathological cardiac hypertrophy.
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spelling pubmed-102296292023-06-01 Long non-coding RNA KCND1 protects hearts from hypertrophy by targeting YBX1 Yang, Rui Li, Liangliang Hou, Yumeng Li, Yingnan Zhang, Jing Yang, Na Zhang, Yuhan Ji, Weihang Yu, Tong Lv, Lifang Liang, Haihai Li, Xuelian Li, Tianyu Shan, Hongli Cell Death Dis Article Cardiac hypertrophy is a common structural remodeling in many cardiovascular diseases. Recently, long non-coding RNAs (LncRNAs) were found to be involved in the physiological and pathological processes of cardiac hypertrophy. In this study, we found that LncRNA KCND1 (LncKCND1) was downregulated in both transverse aortic constriction (TAC)-induced hypertrophic mouse hearts and Angiotensin II (Ang II)-induced neonatal mouse cardiomyocytes. Further analyses showed that the knockdown of LncKCND1 impaired cardiac mitochondrial function and led to hypertrophic changes in cardiomyocytes. In contrast, overexpression of LncKCND1 inhibited Ang II-induced cardiomyocyte hypertrophic changes. Importantly, enhanced expression of LncKCND1 protected the heart from TAC-induced pathological cardiac hypertrophy and improved heart function in TAC mice. Subsequent analyses involving mass spectrometry and RNA immunoprecipitation assays showed that LncKCND1 directly binds to YBX1. Furthermore, overexpression of LncKCND1 upregulated the expression level of YBX1, while silencing LncKCND1 had the opposite effect. Furthermore, YBX1 was downregulated during cardiac hypertrophy, whereas overexpression of YBX1 inhibited Ang II-induced cardiomyocyte hypertrophy. Moreover, silencing YBX1 reversed the effect of LncKCND1 on cardiomyocyte mitochondrial function and its protective role in cardiac hypertrophy, suggesting that YBX1 is a downstream target of LncKCND1 in regulating cardiac hypertrophy. In conclusion, our study provides mechanistic insights into the functioning of LncKCND1 and supports LncKCND1 as a potential therapeutic target for pathological cardiac hypertrophy. Nature Publishing Group UK 2023-05-30 /pmc/articles/PMC10229629/ /pubmed/37253771 http://dx.doi.org/10.1038/s41419-023-05852-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Yang, Rui
Li, Liangliang
Hou, Yumeng
Li, Yingnan
Zhang, Jing
Yang, Na
Zhang, Yuhan
Ji, Weihang
Yu, Tong
Lv, Lifang
Liang, Haihai
Li, Xuelian
Li, Tianyu
Shan, Hongli
Long non-coding RNA KCND1 protects hearts from hypertrophy by targeting YBX1
title Long non-coding RNA KCND1 protects hearts from hypertrophy by targeting YBX1
title_full Long non-coding RNA KCND1 protects hearts from hypertrophy by targeting YBX1
title_fullStr Long non-coding RNA KCND1 protects hearts from hypertrophy by targeting YBX1
title_full_unstemmed Long non-coding RNA KCND1 protects hearts from hypertrophy by targeting YBX1
title_short Long non-coding RNA KCND1 protects hearts from hypertrophy by targeting YBX1
title_sort long non-coding rna kcnd1 protects hearts from hypertrophy by targeting ybx1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10229629/
https://www.ncbi.nlm.nih.gov/pubmed/37253771
http://dx.doi.org/10.1038/s41419-023-05852-7
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