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Novel Transcriptomic Interactomes of Noncoding RNAs in the Heart under Altered Thyroid Hormonal States

Noncoding RNAs are emerging as vital players in cardiovascular diseases. Thyroid hormones (THs) are crucial for cardiovascular survival; however, correction of systemic hypothyroidism (low serum THs) may not improve cardiac tissue-level hypothyroidism or cardiac function. Mechanistically, the unders...

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Autores principales: Rajagopalan, Viswanathan, Chakraborty, Sankalpa, Lin, Richard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10095585/
https://www.ncbi.nlm.nih.gov/pubmed/37047531
http://dx.doi.org/10.3390/ijms24076560
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author Rajagopalan, Viswanathan
Chakraborty, Sankalpa
Lin, Richard
author_facet Rajagopalan, Viswanathan
Chakraborty, Sankalpa
Lin, Richard
author_sort Rajagopalan, Viswanathan
collection PubMed
description Noncoding RNAs are emerging as vital players in cardiovascular diseases. Thyroid hormones (THs) are crucial for cardiovascular survival; however, correction of systemic hypothyroidism (low serum THs) may not improve cardiac tissue-level hypothyroidism or cardiac function. Mechanistically, the understanding of noncoding transcriptomic interactions influencing TH-mediated cardiac effects is unclear. Adult C57BL/6J mixed-sex mice were randomized into Control, Hypothyroid (HypoTH), Hyperthyroid (HyperTH), and HypoTH-Triiodothyronine restoration groups. Physiological, morphological, biochemical, molecular, and whole transcriptomic studies and appropriate statistical analyses were performed. HypoTH showed significant atrophy, depressed cardiac function, and decreased serum THs versus controls, and Triiodothyronine supplementation restored them. HyperTH significantly increased serum THs with hypertrophy. Real-time PCR showed significantly altered inflammatory and immune lncRNAs. The transcriptomic sequencing revealed significant differential expressions of lncRNAs, miRNAs, and mRNAs. Eleven novel circRNAs significantly decreased with increased THs. Multiple pathways were GO-/KEGG-enriched, including cardiac, thyroid, cancer, mitochondrial, inflammatory, adrenergic, metabolic, immune-mediated, vesicular, etc. We also uncovered significant novel co-expression and interactions of lncRNA-miRNA, lncRNA-miRNA-mRNA, lncRNA-mRNA, circRNA-miRNA, and miRNA-mRNA, and splicing events. This includes a novel pathway by which the predominant cardiac TH receptor alpha may interact with specific lncRNAs and miRNAs. This is the first study reporting a comprehensive transcriptome-wide interactome in the cardiac–thyroid axis.
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spelling pubmed-100955852023-04-13 Novel Transcriptomic Interactomes of Noncoding RNAs in the Heart under Altered Thyroid Hormonal States Rajagopalan, Viswanathan Chakraborty, Sankalpa Lin, Richard Int J Mol Sci Article Noncoding RNAs are emerging as vital players in cardiovascular diseases. Thyroid hormones (THs) are crucial for cardiovascular survival; however, correction of systemic hypothyroidism (low serum THs) may not improve cardiac tissue-level hypothyroidism or cardiac function. Mechanistically, the understanding of noncoding transcriptomic interactions influencing TH-mediated cardiac effects is unclear. Adult C57BL/6J mixed-sex mice were randomized into Control, Hypothyroid (HypoTH), Hyperthyroid (HyperTH), and HypoTH-Triiodothyronine restoration groups. Physiological, morphological, biochemical, molecular, and whole transcriptomic studies and appropriate statistical analyses were performed. HypoTH showed significant atrophy, depressed cardiac function, and decreased serum THs versus controls, and Triiodothyronine supplementation restored them. HyperTH significantly increased serum THs with hypertrophy. Real-time PCR showed significantly altered inflammatory and immune lncRNAs. The transcriptomic sequencing revealed significant differential expressions of lncRNAs, miRNAs, and mRNAs. Eleven novel circRNAs significantly decreased with increased THs. Multiple pathways were GO-/KEGG-enriched, including cardiac, thyroid, cancer, mitochondrial, inflammatory, adrenergic, metabolic, immune-mediated, vesicular, etc. We also uncovered significant novel co-expression and interactions of lncRNA-miRNA, lncRNA-miRNA-mRNA, lncRNA-mRNA, circRNA-miRNA, and miRNA-mRNA, and splicing events. This includes a novel pathway by which the predominant cardiac TH receptor alpha may interact with specific lncRNAs and miRNAs. This is the first study reporting a comprehensive transcriptome-wide interactome in the cardiac–thyroid axis. MDPI 2023-03-31 /pmc/articles/PMC10095585/ /pubmed/37047531 http://dx.doi.org/10.3390/ijms24076560 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rajagopalan, Viswanathan
Chakraborty, Sankalpa
Lin, Richard
Novel Transcriptomic Interactomes of Noncoding RNAs in the Heart under Altered Thyroid Hormonal States
title Novel Transcriptomic Interactomes of Noncoding RNAs in the Heart under Altered Thyroid Hormonal States
title_full Novel Transcriptomic Interactomes of Noncoding RNAs in the Heart under Altered Thyroid Hormonal States
title_fullStr Novel Transcriptomic Interactomes of Noncoding RNAs in the Heart under Altered Thyroid Hormonal States
title_full_unstemmed Novel Transcriptomic Interactomes of Noncoding RNAs in the Heart under Altered Thyroid Hormonal States
title_short Novel Transcriptomic Interactomes of Noncoding RNAs in the Heart under Altered Thyroid Hormonal States
title_sort novel transcriptomic interactomes of noncoding rnas in the heart under altered thyroid hormonal states
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10095585/
https://www.ncbi.nlm.nih.gov/pubmed/37047531
http://dx.doi.org/10.3390/ijms24076560
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