Yanbing Lin , Qianwen Zhou , Mengqi Li , Sucheng Hou , Jia Xu , Dongfang Dai , Xiaoqin Yuan
{"title":"丁酸钠激活的LOH12CR2通过mettl14介导的n6 -甲基腺苷修饰SPC24 mRNA抑制结直肠癌的肿瘤发生","authors":"Yanbing Lin , Qianwen Zhou , Mengqi Li , Sucheng Hou , Jia Xu , Dongfang Dai , Xiaoqin Yuan","doi":"10.1016/j.cellsig.2025.112079","DOIUrl":null,"url":null,"abstract":"<div><div>Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Epidemiological studies suggest that dietary fiber intake reduces CRC risk, with butyrate, a fermentation product of dietary fiber, showing promising anti-cancer properties. However, the underlying molecular mechanisms remain poorly understood. In this study, we reveal that sodium butyrate (NaB) upregulates the long non-coding RNA LOH12CR2 in CRC cells, which is crucial for NaB's anti-tumor effects both in vitro and in vivo. Our transcriptome sequencing and subsequent functional analyses demonstrate that LOH12CR2 mediates NaB’s impact by inhibiting the mitotic regulator SPC24, which is overexpressed in CRC. Mechanistically, LOH12CR2 interacts with and stabilizes the m6A methyltransferase METTL14, enhancing m6A modification and subsequent degradation of SPC24 mRNA. We identify a novel LOH12CR2-METTL14-m6A regulatory axis in CRC, through which NaB exerts its anti-tumor effects by downregulating SPC24 post-transcriptionally, thereby suppressing tumor growth and progression. Our findings elucidate a new molecular pathway through which dietary fiber protects against CRC and highlight LOH12CR2 as a potential therapeutic target.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"136 ","pages":"Article 112079"},"PeriodicalIF":3.7000,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"LOH12CR2 activated by sodium butyrate suppresses tumorigenesis in colorectal cancer via METTL14-mediated N6-methyladenosine modification of SPC24 mRNA\",\"authors\":\"Yanbing Lin , Qianwen Zhou , Mengqi Li , Sucheng Hou , Jia Xu , Dongfang Dai , Xiaoqin Yuan\",\"doi\":\"10.1016/j.cellsig.2025.112079\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Epidemiological studies suggest that dietary fiber intake reduces CRC risk, with butyrate, a fermentation product of dietary fiber, showing promising anti-cancer properties. However, the underlying molecular mechanisms remain poorly understood. In this study, we reveal that sodium butyrate (NaB) upregulates the long non-coding RNA LOH12CR2 in CRC cells, which is crucial for NaB's anti-tumor effects both in vitro and in vivo. Our transcriptome sequencing and subsequent functional analyses demonstrate that LOH12CR2 mediates NaB’s impact by inhibiting the mitotic regulator SPC24, which is overexpressed in CRC. Mechanistically, LOH12CR2 interacts with and stabilizes the m6A methyltransferase METTL14, enhancing m6A modification and subsequent degradation of SPC24 mRNA. We identify a novel LOH12CR2-METTL14-m6A regulatory axis in CRC, through which NaB exerts its anti-tumor effects by downregulating SPC24 post-transcriptionally, thereby suppressing tumor growth and progression. Our findings elucidate a new molecular pathway through which dietary fiber protects against CRC and highlight LOH12CR2 as a potential therapeutic target.</div></div>\",\"PeriodicalId\":9902,\"journal\":{\"name\":\"Cellular signalling\",\"volume\":\"136 \",\"pages\":\"Article 112079\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2025-08-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cellular signalling\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0898656825004942\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular signalling","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0898656825004942","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
LOH12CR2 activated by sodium butyrate suppresses tumorigenesis in colorectal cancer via METTL14-mediated N6-methyladenosine modification of SPC24 mRNA
Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Epidemiological studies suggest that dietary fiber intake reduces CRC risk, with butyrate, a fermentation product of dietary fiber, showing promising anti-cancer properties. However, the underlying molecular mechanisms remain poorly understood. In this study, we reveal that sodium butyrate (NaB) upregulates the long non-coding RNA LOH12CR2 in CRC cells, which is crucial for NaB's anti-tumor effects both in vitro and in vivo. Our transcriptome sequencing and subsequent functional analyses demonstrate that LOH12CR2 mediates NaB’s impact by inhibiting the mitotic regulator SPC24, which is overexpressed in CRC. Mechanistically, LOH12CR2 interacts with and stabilizes the m6A methyltransferase METTL14, enhancing m6A modification and subsequent degradation of SPC24 mRNA. We identify a novel LOH12CR2-METTL14-m6A regulatory axis in CRC, through which NaB exerts its anti-tumor effects by downregulating SPC24 post-transcriptionally, thereby suppressing tumor growth and progression. Our findings elucidate a new molecular pathway through which dietary fiber protects against CRC and highlight LOH12CR2 as a potential therapeutic target.
期刊介绍:
Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo.
Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.