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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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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. |
format | Online Article Text |
id | pubmed-10229629 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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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