Lin Du, Geng Xu, Xiuqiang Zhang, Zhiwei Zhang, Yang Yang, Hongsheng Teng, Tao Yang
{"title":"AQP4-AS1 可通过与 miR-4476 竞争性结合来调控肺腺癌中铁蛋白沉积相关调控因子 ALOX15 的表达","authors":"Lin Du, Geng Xu, Xiuqiang Zhang, Zhiwei Zhang, Yang Yang, Hongsheng Teng, Tao Yang","doi":"10.1055/s-0044-1789199","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background</b> The AQP4-AS1/miR-4476-ALOX15 regulatory axis was discovered in previous studies. We aimed to investigate the regulatory mechanism of the ferroptosis-related regulator ALOX15 by AQP4-AS1 and miR-4476 in lung adenocarcinoma (LUAD) and find new targets for clinical treatment. <b>Methods</b> After bioinformatics analysis, we contained one ferroptosis-related gene (FRG), namely ALOX15. MicroRNAs (miRNAs) and long noncoding RNAs were predicted by miRWalk. Furthermore, we constructed overexpressed LUAD cell lines. Real-time quantitative polymerase chain reaction and western blot were used to determine the expression of mRNA and protein, respectively. Cell Counting Kit-8 (CCK-8) and EdU assay were used to detect the cell proliferation. Double luciferase assay was used to detect the binding relationship between AQP4-AS1 and miR-4464. <b>Results</b> ALOX15 was the most significantly downregulated FRG compared with normal tissues. Furthermore, protein-protein interaction network analysis indicated that the AQP4-AS1-miR-4476-ALOX15 regulatory axis might be involved in the occurrence and development of LUAD and there might be direct interaction between AQP4-AS1 and miR-4476, and miR-4476 and ALOX15. Furthermore, AQP4-AS1 and ALOX15 were significantly downregulated in the LUAD tissue and cell lines, whereas miR-4476 showed the opposite results ( <i>p</i> < 0.001). AQP4-AS1 overexpression improved the ALOX15 expression in LUAD cell lines. CCK-8 and EdU assay revealed that overexpression of AQP4-AS1 and ALOX15 inhibited the LUAD cell proliferation. Double luciferase assay results indicated that there was a combination between AQP4-AS1 and miRNA-4476. In addition, we found that overexpressed AQP4-AS1 activates the ferroptosis in LUAD cell lines. <b>Conclusions</b> AQP4-AS1 can regulate the expression of ALOX15 through competitive binding with miR-4476, further activate ferroptosis and inhibit the proliferation of LUAD cells.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 4","pages":"241-250"},"PeriodicalIF":1.5000,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11329318/pdf/","citationCount":"0","resultStr":"{\"title\":\"AQP4-AS1 Can Regulate the Expression of Ferroptosis-Related Regulator ALOX15 through Competitive Binding with miR-4476 in Lung Adenocarcinoma.\",\"authors\":\"Lin Du, Geng Xu, Xiuqiang Zhang, Zhiwei Zhang, Yang Yang, Hongsheng Teng, Tao Yang\",\"doi\":\"10.1055/s-0044-1789199\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Background</b> The AQP4-AS1/miR-4476-ALOX15 regulatory axis was discovered in previous studies. We aimed to investigate the regulatory mechanism of the ferroptosis-related regulator ALOX15 by AQP4-AS1 and miR-4476 in lung adenocarcinoma (LUAD) and find new targets for clinical treatment. <b>Methods</b> After bioinformatics analysis, we contained one ferroptosis-related gene (FRG), namely ALOX15. MicroRNAs (miRNAs) and long noncoding RNAs were predicted by miRWalk. Furthermore, we constructed overexpressed LUAD cell lines. Real-time quantitative polymerase chain reaction and western blot were used to determine the expression of mRNA and protein, respectively. Cell Counting Kit-8 (CCK-8) and EdU assay were used to detect the cell proliferation. Double luciferase assay was used to detect the binding relationship between AQP4-AS1 and miR-4464. <b>Results</b> ALOX15 was the most significantly downregulated FRG compared with normal tissues. Furthermore, protein-protein interaction network analysis indicated that the AQP4-AS1-miR-4476-ALOX15 regulatory axis might be involved in the occurrence and development of LUAD and there might be direct interaction between AQP4-AS1 and miR-4476, and miR-4476 and ALOX15. Furthermore, AQP4-AS1 and ALOX15 were significantly downregulated in the LUAD tissue and cell lines, whereas miR-4476 showed the opposite results ( <i>p</i> < 0.001). AQP4-AS1 overexpression improved the ALOX15 expression in LUAD cell lines. CCK-8 and EdU assay revealed that overexpression of AQP4-AS1 and ALOX15 inhibited the LUAD cell proliferation. Double luciferase assay results indicated that there was a combination between AQP4-AS1 and miRNA-4476. In addition, we found that overexpressed AQP4-AS1 activates the ferroptosis in LUAD cell lines. <b>Conclusions</b> AQP4-AS1 can regulate the expression of ALOX15 through competitive binding with miR-4476, further activate ferroptosis and inhibit the proliferation of LUAD cells.</p>\",\"PeriodicalId\":40142,\"journal\":{\"name\":\"Global Medical Genetics\",\"volume\":\"11 4\",\"pages\":\"241-250\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2024-08-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11329318/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Global Medical Genetics\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1055/s-0044-1789199\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/12/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q4\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Global Medical Genetics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1055/s-0044-1789199","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/1 0:00:00","PubModel":"eCollection","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
AQP4-AS1 Can Regulate the Expression of Ferroptosis-Related Regulator ALOX15 through Competitive Binding with miR-4476 in Lung Adenocarcinoma.
Background The AQP4-AS1/miR-4476-ALOX15 regulatory axis was discovered in previous studies. We aimed to investigate the regulatory mechanism of the ferroptosis-related regulator ALOX15 by AQP4-AS1 and miR-4476 in lung adenocarcinoma (LUAD) and find new targets for clinical treatment. Methods After bioinformatics analysis, we contained one ferroptosis-related gene (FRG), namely ALOX15. MicroRNAs (miRNAs) and long noncoding RNAs were predicted by miRWalk. Furthermore, we constructed overexpressed LUAD cell lines. Real-time quantitative polymerase chain reaction and western blot were used to determine the expression of mRNA and protein, respectively. Cell Counting Kit-8 (CCK-8) and EdU assay were used to detect the cell proliferation. Double luciferase assay was used to detect the binding relationship between AQP4-AS1 and miR-4464. Results ALOX15 was the most significantly downregulated FRG compared with normal tissues. Furthermore, protein-protein interaction network analysis indicated that the AQP4-AS1-miR-4476-ALOX15 regulatory axis might be involved in the occurrence and development of LUAD and there might be direct interaction between AQP4-AS1 and miR-4476, and miR-4476 and ALOX15. Furthermore, AQP4-AS1 and ALOX15 were significantly downregulated in the LUAD tissue and cell lines, whereas miR-4476 showed the opposite results ( p < 0.001). AQP4-AS1 overexpression improved the ALOX15 expression in LUAD cell lines. CCK-8 and EdU assay revealed that overexpression of AQP4-AS1 and ALOX15 inhibited the LUAD cell proliferation. Double luciferase assay results indicated that there was a combination between AQP4-AS1 and miRNA-4476. In addition, we found that overexpressed AQP4-AS1 activates the ferroptosis in LUAD cell lines. Conclusions AQP4-AS1 can regulate the expression of ALOX15 through competitive binding with miR-4476, further activate ferroptosis and inhibit the proliferation of LUAD cells.
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