Long noncoding RNA RMRP ameliorates doxorubicin-induced apoptosis by interacting with PFN1 in a P53-Dependent manner

作者全名："Li, Juexing; Zhou, Lei; Jiang, Yuanliang; Gao, Hailan; Maierhaba, Tuersuntuoheti; Gong, Hui"

作者地址："[Li, Juexing; Zhou, Lei; Gao, Hailan; Maierhaba, Tuersuntuoheti; Gong, Hui] Fudan Univ, Jinshan Hosp, Dept Cardiol, Shanghai 201508, Peoples R China; [Li, Juexing; Zhou, Lei; Gao, Hailan; Maierhaba, Tuersuntuoheti; Gong, Hui] Fudan Univ, Shanghai Med Coll, Dept Internal Med, Shanghai 200032, Peoples R China; [Jiang, Yuanliang] Chongqing Med Univ, Affiliated Hosp 1, Dept Psychiat, Chongqing, Peoples R China; [Gong, Hui] Fudan Univ, Jinshan Hosp, Dept Cardiol, 1508 Longhang Rd, Shanghai 201508, Peoples R China"

通信作者："Gong, H (通讯作者)，Fudan Univ, Jinshan Hosp, Dept Cardiol, 1508 Longhang Rd, Shanghai 201508, Peoples R China."

来源：MOLECULAR AND CELLULAR PROBES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001106741300001

JCR分区：Q3

影响因子：2.3

年份：2023

卷号：72

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Apoptosis; Doxorubicin; Heart failure; LncRNA RMRP; PFN1

摘要："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."

基金机构：Shanghai Science and Technology Commission [19JC1415703]

基金资助正文："<B>Funding</B> This project was funded by the Shanghai Science and Technology Commission, project number 19JC1415703."