Hao Zhang, Ye Han, Chengwei Wu, Siying Wang, Mingquan Chen, Qian Xu, Hong Wei, Xianli Zhou, Guiyu Wang
{"title":"m6a修饰的LINC02418在结直肠癌中通过与YBX1和IGF2BP1相互作用诱导CTNNB1的转录和转录后修饰。","authors":"Hao Zhang, Ye Han, Chengwei Wu, Siying Wang, Mingquan Chen, Qian Xu, Hong Wei, Xianli Zhou, Guiyu Wang","doi":"10.1038/s41420-025-02365-4","DOIUrl":null,"url":null,"abstract":"<p><p>Colorectal cancer (CRC) represents a significant menace to human health, but its molecular pathogenesis remains unclear. Herein, we explored the functional role of LINC02418 in CRC progression. The function of LINC02418 in CRC was determined through vitro and in vivo experiments. The molecular mechanism of LINC02418 in CRC was explored by quantitative real-time PCR (qPCR) analyses, western blot, luciferase reporter assay, methylated RNA immunoprecipitation (MeRIP) assay, RNA pull-down, RNA immunoprecipitation (RIP) assay and chromatin immunoprecipitation (ChIP) assay. The results revealed that LINC02418 expression was upregulated in CRC tissues and the high expression of LINC02418 was related to unfavorable survival of CRC patients. Besides, knockdown of LINC02418 expression resulted in the inhibition of proliferation and metastasis of CRC cells in vitro and in vivo. Mechanistically, we found METTL3-mediated m6A modification induced the aberrant expression of LINC02418 in CRC. LINC02418 could interact with YBX1 and enhance YBX1 DNA-binding ability to the CTNNB1 promoter, resulting in transcriptional activation of CTNNB1. In the post-transcriptional stage, LINC02418 could also enhance CTNNB1 stability by promoting the interaction between IGF2BP1 protein and CTNNB1 mRNA. What is more, LINC02418 expression could be transcriptionally enhanced by YBX1 protein. Collectively, this study unveils a novel oncogenic mechanism for LINC02418 in CRC and the LINC02418 might be a novel therapeutic target in CRC treatment.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"101"},"PeriodicalIF":6.1000,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906587/pdf/","citationCount":"0","resultStr":"{\"title\":\"m6A-modified LINC02418 induces transcriptional and post-transcriptional modification of CTNNB1 via interacting with YBX1 and IGF2BP1 in colorectal cancer.\",\"authors\":\"Hao Zhang, Ye Han, Chengwei Wu, Siying Wang, Mingquan Chen, Qian Xu, Hong Wei, Xianli Zhou, Guiyu Wang\",\"doi\":\"10.1038/s41420-025-02365-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Colorectal cancer (CRC) represents a significant menace to human health, but its molecular pathogenesis remains unclear. Herein, we explored the functional role of LINC02418 in CRC progression. The function of LINC02418 in CRC was determined through vitro and in vivo experiments. The molecular mechanism of LINC02418 in CRC was explored by quantitative real-time PCR (qPCR) analyses, western blot, luciferase reporter assay, methylated RNA immunoprecipitation (MeRIP) assay, RNA pull-down, RNA immunoprecipitation (RIP) assay and chromatin immunoprecipitation (ChIP) assay. The results revealed that LINC02418 expression was upregulated in CRC tissues and the high expression of LINC02418 was related to unfavorable survival of CRC patients. Besides, knockdown of LINC02418 expression resulted in the inhibition of proliferation and metastasis of CRC cells in vitro and in vivo. Mechanistically, we found METTL3-mediated m6A modification induced the aberrant expression of LINC02418 in CRC. LINC02418 could interact with YBX1 and enhance YBX1 DNA-binding ability to the CTNNB1 promoter, resulting in transcriptional activation of CTNNB1. In the post-transcriptional stage, LINC02418 could also enhance CTNNB1 stability by promoting the interaction between IGF2BP1 protein and CTNNB1 mRNA. What is more, LINC02418 expression could be transcriptionally enhanced by YBX1 protein. Collectively, this study unveils a novel oncogenic mechanism for LINC02418 in CRC and the LINC02418 might be a novel therapeutic target in CRC treatment.</p>\",\"PeriodicalId\":9735,\"journal\":{\"name\":\"Cell Death Discovery\",\"volume\":\"11 1\",\"pages\":\"101\"},\"PeriodicalIF\":6.1000,\"publicationDate\":\"2025-03-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906587/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell Death Discovery\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41420-025-02365-4\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Death Discovery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41420-025-02365-4","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
m6A-modified LINC02418 induces transcriptional and post-transcriptional modification of CTNNB1 via interacting with YBX1 and IGF2BP1 in colorectal cancer.
Colorectal cancer (CRC) represents a significant menace to human health, but its molecular pathogenesis remains unclear. Herein, we explored the functional role of LINC02418 in CRC progression. The function of LINC02418 in CRC was determined through vitro and in vivo experiments. The molecular mechanism of LINC02418 in CRC was explored by quantitative real-time PCR (qPCR) analyses, western blot, luciferase reporter assay, methylated RNA immunoprecipitation (MeRIP) assay, RNA pull-down, RNA immunoprecipitation (RIP) assay and chromatin immunoprecipitation (ChIP) assay. The results revealed that LINC02418 expression was upregulated in CRC tissues and the high expression of LINC02418 was related to unfavorable survival of CRC patients. Besides, knockdown of LINC02418 expression resulted in the inhibition of proliferation and metastasis of CRC cells in vitro and in vivo. Mechanistically, we found METTL3-mediated m6A modification induced the aberrant expression of LINC02418 in CRC. LINC02418 could interact with YBX1 and enhance YBX1 DNA-binding ability to the CTNNB1 promoter, resulting in transcriptional activation of CTNNB1. In the post-transcriptional stage, LINC02418 could also enhance CTNNB1 stability by promoting the interaction between IGF2BP1 protein and CTNNB1 mRNA. What is more, LINC02418 expression could be transcriptionally enhanced by YBX1 protein. Collectively, this study unveils a novel oncogenic mechanism for LINC02418 in CRC and the LINC02418 might be a novel therapeutic target in CRC treatment.
期刊介绍：
Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary.
Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.
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