{"title":"沉默核糖体生物发生调节因子1同源物（RRS1）通过激活p53通路介导的铁凋亡抑制肺癌细胞血管生成和顺铂耐药","authors":"Ling Lin , Ying Zou , Di Zhang","doi":"10.1016/j.tice.2025.102796","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Human RRS1 gene is abnormally expressed in many cancers, and RRS1 can inhibit the level of p53. Ferroptosis mediated by p53 pathway may be a potential therapeutic strategy for cancer. However, the specific role of RRS1 in lung cancer is not clear.</div></div><div><h3>Methods</h3><div>The correlation between the expression level of RRS1 and the overall survival of lung cancer patients was explored through UALCAN and Kaplan-Meier plotter. A549 cells and drug-resistant A549/DDP cells were used in vitro. Wound healing, Transwell and tubule formation experiment were used to detect the abilities of cell invasion, migration and tube formation. Detecting the level of lipid ROS by BODIPY(581/591) C11 staining, the expression level of total iron and ferroptosis-related proteins were detected, so as to judge the ferroptosis in cells. Detecting the apoptosis by flow cytometry and the expression of apoptosis-related proteins by western blot, so as to observe the effect of interfering with RRS1 on cisplatin resistance of cells.</div></div><div><h3>Results</h3><div>The expression of RRS1 was up-regulated, and its level was negatively correlated with the overall survival time of lung cancer patients. In vitro experiments showed that RRS1 interference reduced the invasion and migration of lung cancer cells, inhibited the expressions of MMP2 and MMP9 proteins and decreased the tube-forming ability of cells. After interfering with RRS1, the level of p53, lipid ROS and the total iron content in cells increased, the expression of SLC7A11 and GPX4 decreased while the expression of ACSL4 increased, which indicated that ferroptosis was enhanced. Interference with RRS1 increased the apoptosis of drug-resistant cells, decreased the expression of Bcl2 while increased the expression of Bax and caspase3(cleaved), which decreased the cisplatin resistance of lung cancer cell A549. However, after silencing p53, these effects were reversed.</div></div><div><h3>Conclusion</h3><div>RRS1 inhibits angiogenesis and cisplatin resistance of lung cancer cells by activating ferroptosis mediated by p53 pathway.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"94 ","pages":"Article 102796"},"PeriodicalIF":2.5000,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Silencing ribosome biogenesis regulator 1 homolog (RRS1) inhibits angiogenesis and cisplatin resistance of lung cancer cells by activating ferroptosis mediated by p53 pathway\",\"authors\":\"Ling Lin , Ying Zou , Di Zhang\",\"doi\":\"10.1016/j.tice.2025.102796\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Human RRS1 gene is abnormally expressed in many cancers, and RRS1 can inhibit the level of p53. Ferroptosis mediated by p53 pathway may be a potential therapeutic strategy for cancer. However, the specific role of RRS1 in lung cancer is not clear.</div></div><div><h3>Methods</h3><div>The correlation between the expression level of RRS1 and the overall survival of lung cancer patients was explored through UALCAN and Kaplan-Meier plotter. A549 cells and drug-resistant A549/DDP cells were used in vitro. Wound healing, Transwell and tubule formation experiment were used to detect the abilities of cell invasion, migration and tube formation. Detecting the level of lipid ROS by BODIPY(581/591) C11 staining, the expression level of total iron and ferroptosis-related proteins were detected, so as to judge the ferroptosis in cells. Detecting the apoptosis by flow cytometry and the expression of apoptosis-related proteins by western blot, so as to observe the effect of interfering with RRS1 on cisplatin resistance of cells.</div></div><div><h3>Results</h3><div>The expression of RRS1 was up-regulated, and its level was negatively correlated with the overall survival time of lung cancer patients. In vitro experiments showed that RRS1 interference reduced the invasion and migration of lung cancer cells, inhibited the expressions of MMP2 and MMP9 proteins and decreased the tube-forming ability of cells. After interfering with RRS1, the level of p53, lipid ROS and the total iron content in cells increased, the expression of SLC7A11 and GPX4 decreased while the expression of ACSL4 increased, which indicated that ferroptosis was enhanced. Interference with RRS1 increased the apoptosis of drug-resistant cells, decreased the expression of Bcl2 while increased the expression of Bax and caspase3(cleaved), which decreased the cisplatin resistance of lung cancer cell A549. However, after silencing p53, these effects were reversed.</div></div><div><h3>Conclusion</h3><div>RRS1 inhibits angiogenesis and cisplatin resistance of lung cancer cells by activating ferroptosis mediated by p53 pathway.</div></div>\",\"PeriodicalId\":23201,\"journal\":{\"name\":\"Tissue & cell\",\"volume\":\"94 \",\"pages\":\"Article 102796\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2025-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Tissue & cell\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S004081662500076X\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/2/14 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"ANATOMY & MORPHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tissue & cell","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S004081662500076X","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/14 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ANATOMY & MORPHOLOGY","Score":null,"Total":0}
Silencing ribosome biogenesis regulator 1 homolog (RRS1) inhibits angiogenesis and cisplatin resistance of lung cancer cells by activating ferroptosis mediated by p53 pathway
Background
Human RRS1 gene is abnormally expressed in many cancers, and RRS1 can inhibit the level of p53. Ferroptosis mediated by p53 pathway may be a potential therapeutic strategy for cancer. However, the specific role of RRS1 in lung cancer is not clear.
Methods
The correlation between the expression level of RRS1 and the overall survival of lung cancer patients was explored through UALCAN and Kaplan-Meier plotter. A549 cells and drug-resistant A549/DDP cells were used in vitro. Wound healing, Transwell and tubule formation experiment were used to detect the abilities of cell invasion, migration and tube formation. Detecting the level of lipid ROS by BODIPY(581/591) C11 staining, the expression level of total iron and ferroptosis-related proteins were detected, so as to judge the ferroptosis in cells. Detecting the apoptosis by flow cytometry and the expression of apoptosis-related proteins by western blot, so as to observe the effect of interfering with RRS1 on cisplatin resistance of cells.
Results
The expression of RRS1 was up-regulated, and its level was negatively correlated with the overall survival time of lung cancer patients. In vitro experiments showed that RRS1 interference reduced the invasion and migration of lung cancer cells, inhibited the expressions of MMP2 and MMP9 proteins and decreased the tube-forming ability of cells. After interfering with RRS1, the level of p53, lipid ROS and the total iron content in cells increased, the expression of SLC7A11 and GPX4 decreased while the expression of ACSL4 increased, which indicated that ferroptosis was enhanced. Interference with RRS1 increased the apoptosis of drug-resistant cells, decreased the expression of Bcl2 while increased the expression of Bax and caspase3(cleaved), which decreased the cisplatin resistance of lung cancer cell A549. However, after silencing p53, these effects were reversed.
Conclusion
RRS1 inhibits angiogenesis and cisplatin resistance of lung cancer cells by activating ferroptosis mediated by p53 pathway.
期刊介绍：
Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed.
Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.
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