在大鼠细胞衰老模型中,MiR-125b-1-3p 介导的 UQCRB 抑制促进了线粒体代谢紊乱。

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
Sha Lu, Cong'e Tan, Xue Xiao
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引用次数: 0

摘要

背景:细胞衰老与人类衰老和多种衰老相关疾病密切相关,而线粒体能量代谢受损是细胞衰老的一个重要机制。值得注意的是,microRNA-125b-1-3p(miR-125b-1-3p)是一种可能与线粒体能量代谢有关的微RNA(miR,miRNA)。根据生物信息学工具预测,miR-125b-1-3p 可靶向泛醌-细胞色素 c 还原酶结合蛋白(UQCRB)基因,该基因可作为细胞衰老相关疾病的新型诊断指标和治疗靶点,也是延缓衰老的新思路:方法:首先,利用双荧光素酶报告基因检测法确定 UQCRB 为 miR-125b-1-3p 的靶基因。方法:首先,通过双荧光素酶报告基因实验确定 UQCRB 为 miR-125b-1-3p 的靶基因;然后,通过 miRNA 干扰技术验证 miR-125b-1-3p 能负向调控 UQCRB 的表达。随后,通过观察线粒体的内部物质和超微结构,探讨了 miR-125b-1-3p 对线粒体能量代谢功能的影响。此外,研究人员还在大鼠肾小管上皮细胞中建立了细胞衰老的体外模型,并通过检测衰老相关蛋白 p16 和 p21 以及 β-半乳糖苷酶(β-gal)活性对该模型进行了表征。最后,探讨了过氧化氢(H2O2)诱导的细胞线粒体能量代谢功能:实验结果表明,miR-125b-1-3p 通过抑制靶基因 UQCRB 影响线粒体能量代谢功能。同时,H2O2诱导的衰老细胞线粒体能量代谢功能水平低于正常细胞:本研究发现了 miR-125b-1-3p 的靶基因 UQCRB,并证明了它在线粒体能量代谢途径中的作用,以及它可能通过这一途径对细胞衰老产生的影响。对细胞衰老的改善作用可在后续研究中进一步探索,为延缓衰老或治疗衰老相关疾病提供更多选择。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
MiR-125b-1-3p-mediated UQCRB inhibition facilitates mitochondrial metabolism disorders in a rat cellular senescencemodel

Backgroud

Cellular senescence is closely related to human aging and multiple aging-related diseases, and impaired mitochondrial energy metabolism is an important mechanism of cellular senescence. Notably, microRNA-125b-1-3p (miR-125b-1-3p) is a microRNA (miR, miRNA) that may be associated with mitochondrial energy metabolism. Ubiquinol-cytochrome c reductase binding protein (UQCRB) gene, predicted by bioinformatics tools to be targeted by miR-125b-1-3p, could serve as a novel diagnostic indicator and therapeutic target for cellular senescence-associated diseases, as well as a new idea for delaying aging.

Methods

First, the dual-luciferase reporter gene assay was used to identify UQCRB as a target gene of miR-125b-1-3p. Next, miRNA interference technology was conducted to verify that miR-125b-1-3p could negatively regulate the expression of UQCRB. Subsequently, the influence of miR-125b-1-3p on mitochondrial energy metabolism function was explored by observing the internal substances and ultrastructure of mitochondria. Further, an in vitro model of cellular senescence was established in rat renal tubular epithelial cells, which was characterized by detecting senescence-related proteins p16 and p21 and beta-galactosidase (β-gal) activity. Finally, the mitochondrial energy metabolism function of hydrogen peroxide (H2O2)-incubated cells was explored.

Results

The experimental results revealed that miR-125b-1-3p affected the mitochondrial energy metabolism function by inhibiting the target gene UQCRB. Meanwhile, the level of mitochondrial energy metabolism function in H2O2-incubated senescent cells was lower than that in normal cells.

Conclusion

In this study, we identified the target gene, UQCRB, of miR-125b-1-3p, and demonstrated its role in the pathway of mitochondrial energy metabolism, as well as its possible effect on cellular senescence through this pathway. The ameliorative effects on cellular senescence can be further explored in subsequent studies to provide additional options for delaying aging or treating aging-related diseases.

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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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