RNA sequencing reveals novel LncRNA/mRNAs co-expression network associated with puerarin-mediated inhibition of cardiac hypertrophy in mice

Background Evidence has demonstrated that puerarin is a potential medicine for the treatment of cardiac hypertrophy. However, the precise underlying molecular mechanisms of the protective effect of puerarin are still unclear. Here, we aimed to explore the regulatory mechanisms of lncRNAs/mRNAs co-ex...

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Main Authors: Shan Ye, Weiyan Chen, Caiwen Ou, Min-Sheng Chen
Format: Article
Language:English
Published: PeerJ Inc. 2022-04-01
Series:PeerJ
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Online Access:https://peerj.com/articles/13144.pdf
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author Shan Ye
Weiyan Chen
Caiwen Ou
Min-Sheng Chen
author_facet Shan Ye
Weiyan Chen
Caiwen Ou
Min-Sheng Chen
author_sort Shan Ye
collection DOAJ
description Background Evidence has demonstrated that puerarin is a potential medicine for the treatment of cardiac hypertrophy. However, the precise underlying molecular mechanisms of the protective effect of puerarin are still unclear. Here, we aimed to explore the regulatory mechanisms of lncRNAs/mRNAs co-expression network in a cardiac hypertrophy mouse model after puerarin treatment. Methods A mouse model of cardiac hypertrophy was established by transverse aortic constriction (TAC). The echocardiography, tissue staining and western blot were used to examine the protective effect of puerarin. Then RNA sequencing (RNA-seq) was carried out to analyze systematically mRNAs and lncRNAs expression. The target lncRNA were confirmed using qRT-PCR. Moreover, a coding/non-coding gene co-expression network were established to find the interaction of lncRNA and mRNAs. The biological process, cellular component, molecular function and pathways of different expression mRNAs targeted by lncRNA were explored using Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis. Results Puerarin exhibited an obvious inhibitory effect in cardiac hypertrophy in TAC model. RNA-seq analysis was performed to investigate the lncRNAs and mRNAs expression patterns of cardiomyocytes in sham and TAC groups treated with or without puerarin. RNA-seq identified that TAC downregulated four lncRNAs, which could be revised by puerarin treatment (|log2 Fold change| > 2 and FDR < 0.05). Among them, expression alterations of lncRNA Airn (antisense of Igf2r non-protein coding RNA) was confirmed by qRT-PCR. Pearson’s correlation coefficients of co-expression levels suggested that there was an interactive relationship between Airn and 2,387 mRNAs (r > 0.95 or r < −0.95). Those co-expressed mRNAs were enriched in some important biological processes such as translational initiation, cell proliferation, insulin-like growth factor binding and poly(A) RNA binding. KEGG analyses suggested that those Airn-interacted mRNAs were enriched in endocytosis, signaling pathways regulating pluripotency of stem cells and the Jak-STAT pathway. Conclusion Puerarin may exert beneficial effects on cardiac hypertrophy through regulating the lncRNAs/mRNAs co-expression network.
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spelling doaj.art-1f1e815aac7843d5a8cf768a12858ca62023-12-03T10:03:28ZengPeerJ Inc.PeerJ2167-83592022-04-0110e1314410.7717/peerj.13144RNA sequencing reveals novel LncRNA/mRNAs co-expression network associated with puerarin-mediated inhibition of cardiac hypertrophy in miceShan Ye0Weiyan Chen1Caiwen Ou2Min-Sheng Chen3Department of Cardiology, Laboratory of Heart Center, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Zhujiang Hospital, Southern Medical University, Guangzhou, PR ChinaIntensive Care Unit, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, ChinaDongguan Hospital of Southern Medical University, Dongguan, Guangdong, ChinaDepartment of Cardiology, Laboratory of Heart Center, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Zhujiang Hospital, Southern Medical University, Guangzhou, PR ChinaBackground Evidence has demonstrated that puerarin is a potential medicine for the treatment of cardiac hypertrophy. However, the precise underlying molecular mechanisms of the protective effect of puerarin are still unclear. Here, we aimed to explore the regulatory mechanisms of lncRNAs/mRNAs co-expression network in a cardiac hypertrophy mouse model after puerarin treatment. Methods A mouse model of cardiac hypertrophy was established by transverse aortic constriction (TAC). The echocardiography, tissue staining and western blot were used to examine the protective effect of puerarin. Then RNA sequencing (RNA-seq) was carried out to analyze systematically mRNAs and lncRNAs expression. The target lncRNA were confirmed using qRT-PCR. Moreover, a coding/non-coding gene co-expression network were established to find the interaction of lncRNA and mRNAs. The biological process, cellular component, molecular function and pathways of different expression mRNAs targeted by lncRNA were explored using Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis. Results Puerarin exhibited an obvious inhibitory effect in cardiac hypertrophy in TAC model. RNA-seq analysis was performed to investigate the lncRNAs and mRNAs expression patterns of cardiomyocytes in sham and TAC groups treated with or without puerarin. RNA-seq identified that TAC downregulated four lncRNAs, which could be revised by puerarin treatment (|log2 Fold change| > 2 and FDR < 0.05). Among them, expression alterations of lncRNA Airn (antisense of Igf2r non-protein coding RNA) was confirmed by qRT-PCR. Pearson’s correlation coefficients of co-expression levels suggested that there was an interactive relationship between Airn and 2,387 mRNAs (r > 0.95 or r < −0.95). Those co-expressed mRNAs were enriched in some important biological processes such as translational initiation, cell proliferation, insulin-like growth factor binding and poly(A) RNA binding. KEGG analyses suggested that those Airn-interacted mRNAs were enriched in endocytosis, signaling pathways regulating pluripotency of stem cells and the Jak-STAT pathway. Conclusion Puerarin may exert beneficial effects on cardiac hypertrophy through regulating the lncRNAs/mRNAs co-expression network.https://peerj.com/articles/13144.pdfLong non-coding RNAMessage RNARNA sequencingCardiac hypertrophyPuerarin
spellingShingle Shan Ye
Weiyan Chen
Caiwen Ou
Min-Sheng Chen
RNA sequencing reveals novel LncRNA/mRNAs co-expression network associated with puerarin-mediated inhibition of cardiac hypertrophy in mice
PeerJ
Long non-coding RNA
Message RNA
RNA sequencing
Cardiac hypertrophy
Puerarin
title RNA sequencing reveals novel LncRNA/mRNAs co-expression network associated with puerarin-mediated inhibition of cardiac hypertrophy in mice
title_full RNA sequencing reveals novel LncRNA/mRNAs co-expression network associated with puerarin-mediated inhibition of cardiac hypertrophy in mice
title_fullStr RNA sequencing reveals novel LncRNA/mRNAs co-expression network associated with puerarin-mediated inhibition of cardiac hypertrophy in mice
title_full_unstemmed RNA sequencing reveals novel LncRNA/mRNAs co-expression network associated with puerarin-mediated inhibition of cardiac hypertrophy in mice
title_short RNA sequencing reveals novel LncRNA/mRNAs co-expression network associated with puerarin-mediated inhibition of cardiac hypertrophy in mice
title_sort rna sequencing reveals novel lncrna mrnas co expression network associated with puerarin mediated inhibition of cardiac hypertrophy in mice
topic Long non-coding RNA
Message RNA
RNA sequencing
Cardiac hypertrophy
Puerarin
url https://peerj.com/articles/13144.pdf
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