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

IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS
Juexing Li , Lei Zhou , Yuanliang Jiang , Hailan Gao , Tuersuntuoheti Maierhaba , Hui Gong
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引用次数: 1

Abstract

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.

Abstract Image

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。
阿霉素(DOX)在应用过程中经常引起急性或慢性心脏毒性。据报道,LncRNA-RMRP与几种生物学过程有关,如软骨毛发育不全,但RMRP与DOX诱导的心脏毒性和慢性心力衰竭之间的关系尚不清楚。为了验证这一假设,对GSE124401和GSE149870进行了生物信息学处理,然后在21名心力衰竭患者的外周血中与7名对照组相比验证了差异表达的RMRP。对于体外验证,我们使用了AC16和HEK-293T细胞。用qPCR检测mRNA的表达水平。Western blot和TUNEL染色检测细胞凋亡程度。此外,RMRP和PFN1 mRNA之间的相互作用通过双荧光素酶报告基因测定得到了验证。在生物信息学中,RMRP表现出显著的下调,这在临床样本中得到了验证(p
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来源期刊
Molecular and Cellular Probes
Molecular and Cellular Probes 生物-生化研究方法
CiteScore
6.80
自引率
0.00%
发文量
52
审稿时长
16 days
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.
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