{"title":"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。","authors":"Sha Lu, Cong'e Tan, Xue Xiao","doi":"10.1016/j.mcp.2024.101979","DOIUrl":null,"url":null,"abstract":"<div><h3>Backgroud</h3><p>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 (<em>UQCRB</em>) 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.</p></div><div><h3>Methods</h3><p>First, the dual-luciferase reporter gene assay was used to identify <em>UQCRB</em> 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 <em>UQCRB</em>. 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 <em>in vitro</em> 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 (H<sub>2</sub>O<sub>2</sub>)-incubated cells was explored.</p></div><div><h3>Results</h3><p>The experimental results revealed that miR-125b-1-3p affected the mitochondrial energy metabolism function by inhibiting the target gene <em>UQCRB.</em> Meanwhile, the level of mitochondrial energy metabolism function in H<sub>2</sub>O<sub>2</sub>-incubated senescent cells was lower than that in normal cells.</p></div><div><h3>Conclusion</h3><p>In this study, we identified the target gene, <em>UQCRB</em>, 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.</p></div>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850824000318/pdfft?md5=2f164a8a41a33e01fed76a3bd1c7f0e6&pid=1-s2.0-S0890850824000318-main.pdf","citationCount":"0","resultStr":"{\"title\":\"MiR-125b-1-3p-mediated UQCRB inhibition facilitates mitochondrial metabolism disorders in a rat cellular senescencemodel\",\"authors\":\"Sha Lu, Cong'e Tan, Xue Xiao\",\"doi\":\"10.1016/j.mcp.2024.101979\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Backgroud</h3><p>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 (<em>UQCRB</em>) 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.</p></div><div><h3>Methods</h3><p>First, the dual-luciferase reporter gene assay was used to identify <em>UQCRB</em> 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 <em>UQCRB</em>. 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 <em>in vitro</em> 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 (H<sub>2</sub>O<sub>2</sub>)-incubated cells was explored.</p></div><div><h3>Results</h3><p>The experimental results revealed that miR-125b-1-3p affected the mitochondrial energy metabolism function by inhibiting the target gene <em>UQCRB.</em> Meanwhile, the level of mitochondrial energy metabolism function in H<sub>2</sub>O<sub>2</sub>-incubated senescent cells was lower than that in normal cells.</p></div><div><h3>Conclusion</h3><p>In this study, we identified the target gene, <em>UQCRB</em>, 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.</p></div>\",\"PeriodicalId\":2,\"journal\":{\"name\":\"ACS Applied Bio Materials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-08-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0890850824000318/pdfft?md5=2f164a8a41a33e01fed76a3bd1c7f0e6&pid=1-s2.0-S0890850824000318-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Applied Bio Materials\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0890850824000318\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MATERIALS SCIENCE, BIOMATERIALS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0890850824000318","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
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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