Long noncoding RNA RMRP ameliorates doxorubicin-induced apoptosis by interacting with PFN1 in a P53-Dependent manner
Doxorubicin (DOX) often causes acute or chronic cardiotoxicity during its application. LncRNA RMRP has been reported to be associated with several biological processes, such as cartilage-hair hypoplasia, but the relationship between RMRP and DOX-induced cardiotoxicity and chronic heart failure remai...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Molecular and Cellular Probes |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0890850823000464 |
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| author | Juexing Li Lei Zhou Yuanliang Jiang Hailan Gao Tuersuntuoheti Maierhaba Hui Gong |
| author_facet | Juexing Li Lei Zhou Yuanliang Jiang Hailan Gao Tuersuntuoheti Maierhaba Hui Gong |
| author_sort | Juexing Li |
| collection | DOAJ |
| description | Doxorubicin (DOX) often causes acute or chronic cardiotoxicity during its application. LncRNA RMRP has been reported to be associated with several biological processes, such as cartilage-hair hypoplasia, but the relationship between RMRP and DOX-induced cardiotoxicity and chronic heart failure remains obscure. To test this hypothesis, GSE124401 and GSE149870 were processed for bioinformatics, and differentially expressed RMRP was then verified in the peripheral blood of 21 patients with heart failure compared with 7 controls. For in vitro validation, we used AC16 and HEK-293T cells. qPCR was used to detect the mRNA expression levels. The degree of apoptosis was detected by Western blot and TUNEL staining. Furthermore, the interaction between RMRP and PFN1 mRNA was verified by dual-luciferase reporter assays. In bioinformatics, RMRP showed significant downregulation, which was verified in clinical samples (p < 0.001) and DOX-treated AC16 models (p < 0.0001). Next, overexpression of RMRP could significantly alleviate DOX-induced apoptosis, and a potential downstream molecule of RMRP, PFN1, was also negatively associated with this change. RESCUE experiments further confirmed that PFN1 could be regulated by RMRP at both the RNA and protein levels, serving as a downstream mediator of RMRP's cardioprotective effects. This interaction was then confirmed to be a direct combination (p < 0.0001). Finally, we found that overexpression of RMRP could inhibit the expression of p53 and its phosphorylation level by suppressing PFN1. In summary, RMRP could exert cardioprotective effects via the PFN1/p53 axis, holding great promise for serving as a therapeutic target and potential biomarker. |
| first_indexed | 2024-03-09T03:11:07Z |
| format | Article |
| id | doaj.art-9232c2e59a3d4e3ca73350d28abecd05 |
| institution | Directory Open Access Journal |
| issn | 0890-8508 |
| language | English |
| last_indexed | 2024-03-09T03:11:07Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular and Cellular Probes |
| spelling | doaj.art-9232c2e59a3d4e3ca73350d28abecd052023-12-04T05:21:21ZengElsevierMolecular and Cellular Probes0890-85082023-12-0172101937Long noncoding RNA RMRP ameliorates doxorubicin-induced apoptosis by interacting with PFN1 in a P53-Dependent mannerJuexing Li0Lei Zhou1Yuanliang Jiang2Hailan Gao3Tuersuntuoheti Maierhaba4Hui Gong5Department of Cardiology, Jinshan Hospital of Fudan University, Shanghai, 201508, China; Department of Internal Medicine, Shanghai Medical College, Fudan University, Shanghai, 200032, ChinaDepartment of Cardiology, Jinshan Hospital of Fudan University, Shanghai, 201508, China; Department of Internal Medicine, Shanghai Medical College, Fudan University, Shanghai, 200032, ChinaDepartment of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Cardiology, Jinshan Hospital of Fudan University, Shanghai, 201508, China; Department of Internal Medicine, Shanghai Medical College, Fudan University, Shanghai, 200032, ChinaDepartment of Cardiology, Jinshan Hospital of Fudan University, Shanghai, 201508, China; Department of Internal Medicine, Shanghai Medical College, Fudan University, Shanghai, 200032, ChinaDepartment of Cardiology, Jinshan Hospital of Fudan University, Shanghai, 201508, China; Department of Internal Medicine, Shanghai Medical College, Fudan University, Shanghai, 200032, China; Corresponding author. Department of Cardiology, Jinshan Hospital of Fudan University, 1508 Longhang Road, Jinshan District, Shanghai, 201508, China.Doxorubicin (DOX) often causes acute or chronic cardiotoxicity during its application. LncRNA RMRP has been reported to be associated with several biological processes, such as cartilage-hair hypoplasia, but the relationship between RMRP and DOX-induced cardiotoxicity and chronic heart failure remains obscure. To test this hypothesis, GSE124401 and GSE149870 were processed for bioinformatics, and differentially expressed RMRP was then verified in the peripheral blood of 21 patients with heart failure compared with 7 controls. For in vitro validation, we used AC16 and HEK-293T cells. qPCR was used to detect the mRNA expression levels. The degree of apoptosis was detected by Western blot and TUNEL staining. Furthermore, the interaction between RMRP and PFN1 mRNA was verified by dual-luciferase reporter assays. In bioinformatics, RMRP showed significant downregulation, which was verified in clinical samples (p < 0.001) and DOX-treated AC16 models (p < 0.0001). Next, overexpression of RMRP could significantly alleviate DOX-induced apoptosis, and a potential downstream molecule of RMRP, PFN1, was also negatively associated with this change. RESCUE experiments further confirmed that PFN1 could be regulated by RMRP at both the RNA and protein levels, serving as a downstream mediator of RMRP's cardioprotective effects. This interaction was then confirmed to be a direct combination (p < 0.0001). Finally, we found that overexpression of RMRP could inhibit the expression of p53 and its phosphorylation level by suppressing PFN1. In summary, RMRP could exert cardioprotective effects via the PFN1/p53 axis, holding great promise for serving as a therapeutic target and potential biomarker.http://www.sciencedirect.com/science/article/pii/S0890850823000464ApoptosisDoxorubicinHeart failureLncRNA RMRPPFN1 |
| spellingShingle | Juexing Li Lei Zhou Yuanliang Jiang Hailan Gao Tuersuntuoheti Maierhaba Hui Gong Long noncoding RNA RMRP ameliorates doxorubicin-induced apoptosis by interacting with PFN1 in a P53-Dependent manner Molecular and Cellular Probes Apoptosis Doxorubicin Heart failure LncRNA RMRP PFN1 |
| title | Long noncoding RNA RMRP ameliorates doxorubicin-induced apoptosis by interacting with PFN1 in a P53-Dependent manner |
| title_full | Long noncoding RNA RMRP ameliorates doxorubicin-induced apoptosis by interacting with PFN1 in a P53-Dependent manner |
| title_fullStr | Long noncoding RNA RMRP ameliorates doxorubicin-induced apoptosis by interacting with PFN1 in a P53-Dependent manner |
| title_full_unstemmed | Long noncoding RNA RMRP ameliorates doxorubicin-induced apoptosis by interacting with PFN1 in a P53-Dependent manner |
| title_short | Long noncoding RNA RMRP ameliorates doxorubicin-induced apoptosis by interacting with PFN1 in a P53-Dependent manner |
| title_sort | long noncoding rna rmrp ameliorates doxorubicin induced apoptosis by interacting with pfn1 in a p53 dependent manner |
| topic | Apoptosis Doxorubicin Heart failure LncRNA RMRP PFN1 |
| url | http://www.sciencedirect.com/science/article/pii/S0890850823000464 |
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