Circular PVT1 promotes cardiac fibroblast activation interacting with miR-30a-5p and miR-125b-5p
Abstract Circular RNAs (circRNAs) are involved in the pathogenesis of several cardiovascular diseases, including heart failure. In this study, we report that circular PVT1 (circPVT1) was upregulated in the left ventricle of 31 ischemic heart failure patients compared to 11 non-ischemic controls. RNA...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-04-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07652-7 |
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| author | Alessia Bibi Alisia Madè Simona Greco Jose Manuel Garcia-Manteiga Anna Sofia Tascini Spyros Tastsoglou Germana Zaccagnini Przemyslaw Leszek Carlo Gaetano Fabio Martelli |
| author_facet | Alessia Bibi Alisia Madè Simona Greco Jose Manuel Garcia-Manteiga Anna Sofia Tascini Spyros Tastsoglou Germana Zaccagnini Przemyslaw Leszek Carlo Gaetano Fabio Martelli |
| author_sort | Alessia Bibi |
| collection | DOAJ |
| description | Abstract Circular RNAs (circRNAs) are involved in the pathogenesis of several cardiovascular diseases, including heart failure. In this study, we report that circular PVT1 (circPVT1) was upregulated in the left ventricle of 31 ischemic heart failure patients compared to 11 non-ischemic controls. RNA sequencing analysis following circPVT1 knockdown in immortalized human cardiomyocytes identified differentially expressed genes, mainly involved in fibrosis. Notably, in human cardiac fibroblasts, circPVT1 expression significantly increased after TGF-β1 treatment and circPVT1 silencing attenuated the levels of pro-fibrotic markers induced by TGF-β1. RNA pull-down assays validated the interaction between circPVT1 and two fibrosis-related miRNAs, miR-30a-5p and miR-125b-5p. The levels of these miRNAs were not altered upon circPVT1 knockdown. However, the expression of their mRNA targets was deregulated upon circPVT1 silencing, suggesting that circPVT1 modulates miRNA cellular bioavailability. Accordingly, inhibition of either miR-30a-5p or miR-125b-5p restored the expression of TGF-β1-induced pro-fibrotic markers following circPVT1 silencing, indicating that both miR-30a-5p and miR-125b-5p act as downstream effectors of circPVT1 in cardiac fibroblast activation. In conclusion, these findings highlight a pro-fibrotic role for circPVT1, which can regulate cardiac fibroblast activation interacting with the anti-fibrotic miR-30a-5p and miR-125b-5p. The modulation of circPVT1 expression may represent a potential strategy to reduce cardiac fibrosis and remodeling. |
| format | Article |
| id | doaj-art-77ffbb8320cf4add9756f6ea0258454f |
| institution | DOAJ |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-77ffbb8320cf4add9756f6ea0258454f2025-08-20T03:15:12ZengNature Publishing GroupCell Death and Disease2041-48892025-04-0116111210.1038/s41419-025-07652-7Circular PVT1 promotes cardiac fibroblast activation interacting with miR-30a-5p and miR-125b-5pAlessia Bibi0Alisia Madè1Simona Greco2Jose Manuel Garcia-Manteiga3Anna Sofia Tascini4Spyros Tastsoglou5Germana Zaccagnini6Przemyslaw Leszek7Carlo Gaetano8Fabio Martelli9Molecular Cardiology Laboratory, IRCCS Policlinico San Donato, San Donato MilaneseMolecular Cardiology Laboratory, IRCCS Policlinico San Donato, San Donato MilaneseMolecular Cardiology Laboratory, IRCCS Policlinico San Donato, San Donato MilaneseCenter for Omics Sciences, IRCCS Ospedale San RaffaeleCenter for Omics Sciences, IRCCS Ospedale San RaffaeleMolecular Cardiology Laboratory, IRCCS Policlinico San Donato, San Donato MilaneseMolecular Cardiology Laboratory, IRCCS Policlinico San Donato, San Donato MilaneseDepartment of Heart Failure and Transplantology, Department of Mechanical Circulatory Support and Transplant, National Institute of CardiologyLaboratory of Epigenetics, Istituti Clinici Scientifici Maugeri IRCCSMolecular Cardiology Laboratory, IRCCS Policlinico San Donato, San Donato MilaneseAbstract Circular RNAs (circRNAs) are involved in the pathogenesis of several cardiovascular diseases, including heart failure. In this study, we report that circular PVT1 (circPVT1) was upregulated in the left ventricle of 31 ischemic heart failure patients compared to 11 non-ischemic controls. RNA sequencing analysis following circPVT1 knockdown in immortalized human cardiomyocytes identified differentially expressed genes, mainly involved in fibrosis. Notably, in human cardiac fibroblasts, circPVT1 expression significantly increased after TGF-β1 treatment and circPVT1 silencing attenuated the levels of pro-fibrotic markers induced by TGF-β1. RNA pull-down assays validated the interaction between circPVT1 and two fibrosis-related miRNAs, miR-30a-5p and miR-125b-5p. The levels of these miRNAs were not altered upon circPVT1 knockdown. However, the expression of their mRNA targets was deregulated upon circPVT1 silencing, suggesting that circPVT1 modulates miRNA cellular bioavailability. Accordingly, inhibition of either miR-30a-5p or miR-125b-5p restored the expression of TGF-β1-induced pro-fibrotic markers following circPVT1 silencing, indicating that both miR-30a-5p and miR-125b-5p act as downstream effectors of circPVT1 in cardiac fibroblast activation. In conclusion, these findings highlight a pro-fibrotic role for circPVT1, which can regulate cardiac fibroblast activation interacting with the anti-fibrotic miR-30a-5p and miR-125b-5p. The modulation of circPVT1 expression may represent a potential strategy to reduce cardiac fibrosis and remodeling.https://doi.org/10.1038/s41419-025-07652-7 |
| spellingShingle | Alessia Bibi Alisia Madè Simona Greco Jose Manuel Garcia-Manteiga Anna Sofia Tascini Spyros Tastsoglou Germana Zaccagnini Przemyslaw Leszek Carlo Gaetano Fabio Martelli Circular PVT1 promotes cardiac fibroblast activation interacting with miR-30a-5p and miR-125b-5p Cell Death and Disease |
| title | Circular PVT1 promotes cardiac fibroblast activation interacting with miR-30a-5p and miR-125b-5p |
| title_full | Circular PVT1 promotes cardiac fibroblast activation interacting with miR-30a-5p and miR-125b-5p |
| title_fullStr | Circular PVT1 promotes cardiac fibroblast activation interacting with miR-30a-5p and miR-125b-5p |
| title_full_unstemmed | Circular PVT1 promotes cardiac fibroblast activation interacting with miR-30a-5p and miR-125b-5p |
| title_short | Circular PVT1 promotes cardiac fibroblast activation interacting with miR-30a-5p and miR-125b-5p |
| title_sort | circular pvt1 promotes cardiac fibroblast activation interacting with mir 30a 5p and mir 125b 5p |
| url | https://doi.org/10.1038/s41419-025-07652-7 |
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