Juexing Li , Lei Zhou , Yuanliang Jiang , Hailan Gao , Tuersuntuoheti Maierhaba , Hui Gong
{"title":"长非编码RNA RMRP通过与PFN1以P53依赖的方式相互作用来改善阿霉素诱导的细胞凋亡。","authors":"Juexing Li , Lei Zhou , Yuanliang Jiang , Hailan Gao , Tuersuntuoheti Maierhaba , Hui Gong","doi":"10.1016/j.mcp.2023.101937","DOIUrl":null,"url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"72 ","pages":"Article 101937"},"PeriodicalIF":2.3000,"publicationDate":"2023-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Long noncoding RNA RMRP ameliorates doxorubicin-induced apoptosis by interacting with PFN1 in a P53-Dependent manner\",\"authors\":\"Juexing Li , Lei Zhou , Yuanliang Jiang , Hailan Gao , Tuersuntuoheti Maierhaba , Hui Gong\",\"doi\":\"10.1016/j.mcp.2023.101937\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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.</p></div>\",\"PeriodicalId\":49799,\"journal\":{\"name\":\"Molecular and Cellular Probes\",\"volume\":\"72 \",\"pages\":\"Article 101937\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2023-10-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular and Cellular Probes\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0890850823000464\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular and Cellular Probes","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0890850823000464","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
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 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.
期刊介绍:
MCP - Advancing biology through–omics and bioinformatic technologies wants to capture outcomes from the current revolution in molecular technologies and sciences. The journal has broadened its scope and embraces any high quality research papers, reviews and opinions in areas including, but not limited to, molecular biology, cell biology, biochemistry, immunology, physiology, epidemiology, ecology, virology, microbiology, parasitology, genetics, evolutionary biology, genomics (including metagenomics), bioinformatics, proteomics, metabolomics, glycomics, and lipidomics. Submissions with a technology-driven focus on understanding normal biological or disease processes as well as conceptual advances and paradigm shifts are particularly encouraged. The Editors welcome fundamental or applied research areas; pre-submission enquiries about advanced draft manuscripts are welcomed. Top quality research and manuscripts will be fast-tracked.