Yan Zhong, Jingfeng Liu, Wenwen Lin, Tian Peng, Lingfang Gao, Lan Shen, Ping Wang, Zhiyan Hu, Ting Long, Zuguo Li, Jingquan Liu
{"title":"通过m6A读取器IGF2BP3稳定OLFML1通过Hedgehog通路激活CRC驱动CSC特性","authors":"Yan Zhong, Jingfeng Liu, Wenwen Lin, Tian Peng, Lingfang Gao, Lan Shen, Ping Wang, Zhiyan Hu, Ting Long, Zuguo Li, Jingquan Liu","doi":"10.7150/ijbs.111032","DOIUrl":null,"url":null,"abstract":"<p><p>Colorectal cancer (CRC) progression is closely associated with cancer stemness, which contributes to poor prognosis and therapeutic resistance. This study identifies OLFML1 as a key target accounting for CRC progression. High expression of OLFML1 promotes CRC cell proliferation and cancer stemness. As for mechanism study, we further revealed that IGF2BP3 as a critical up-stream regulator of OLFML1. Our study indicated that IGF2BP3 stabilizes OLFML1 mRNA through m<sup>6</sup>A modification, thereby enhancing its expression. In addition, IGF2BP3 prevents OLFML1 degradation via the ubiquitin-proteasome pathway. Clinically, this study demonstrated a positive association between IGF2BP3 and OLFML1 in CRC patient samples. High co-expression of IGF2BP3 and OLFML1 was significantly correlated with larger tumor size and advanced T stage. These findings highlight the IGF2BP3/OLFML1 axis as a potential driver of CRC stemness and Hedgehog pathway activation, offering promising prognostic and therapeutic targets for CRC management.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 10","pages":"4334-4352"},"PeriodicalIF":10.0000,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320246/pdf/","citationCount":"0","resultStr":"{\"title\":\"Stabilization of OLFML1 via m<sup>6</sup>A Reader IGF2BP3 Drives CSC Characteristics Through Hedgehog Pathway Activation in CRC.\",\"authors\":\"Yan Zhong, Jingfeng Liu, Wenwen Lin, Tian Peng, Lingfang Gao, Lan Shen, Ping Wang, Zhiyan Hu, Ting Long, Zuguo Li, Jingquan Liu\",\"doi\":\"10.7150/ijbs.111032\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Colorectal cancer (CRC) progression is closely associated with cancer stemness, which contributes to poor prognosis and therapeutic resistance. This study identifies OLFML1 as a key target accounting for CRC progression. High expression of OLFML1 promotes CRC cell proliferation and cancer stemness. As for mechanism study, we further revealed that IGF2BP3 as a critical up-stream regulator of OLFML1. Our study indicated that IGF2BP3 stabilizes OLFML1 mRNA through m<sup>6</sup>A modification, thereby enhancing its expression. In addition, IGF2BP3 prevents OLFML1 degradation via the ubiquitin-proteasome pathway. Clinically, this study demonstrated a positive association between IGF2BP3 and OLFML1 in CRC patient samples. High co-expression of IGF2BP3 and OLFML1 was significantly correlated with larger tumor size and advanced T stage. These findings highlight the IGF2BP3/OLFML1 axis as a potential driver of CRC stemness and Hedgehog pathway activation, offering promising prognostic and therapeutic targets for CRC management.</p>\",\"PeriodicalId\":13762,\"journal\":{\"name\":\"International Journal of Biological Sciences\",\"volume\":\"21 10\",\"pages\":\"4334-4352\"},\"PeriodicalIF\":10.0000,\"publicationDate\":\"2025-06-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320246/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Biological Sciences\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.7150/ijbs.111032\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Biological Sciences","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.7150/ijbs.111032","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Stabilization of OLFML1 via m6A Reader IGF2BP3 Drives CSC Characteristics Through Hedgehog Pathway Activation in CRC.
Colorectal cancer (CRC) progression is closely associated with cancer stemness, which contributes to poor prognosis and therapeutic resistance. This study identifies OLFML1 as a key target accounting for CRC progression. High expression of OLFML1 promotes CRC cell proliferation and cancer stemness. As for mechanism study, we further revealed that IGF2BP3 as a critical up-stream regulator of OLFML1. Our study indicated that IGF2BP3 stabilizes OLFML1 mRNA through m6A modification, thereby enhancing its expression. In addition, IGF2BP3 prevents OLFML1 degradation via the ubiquitin-proteasome pathway. Clinically, this study demonstrated a positive association between IGF2BP3 and OLFML1 in CRC patient samples. High co-expression of IGF2BP3 and OLFML1 was significantly correlated with larger tumor size and advanced T stage. These findings highlight the IGF2BP3/OLFML1 axis as a potential driver of CRC stemness and Hedgehog pathway activation, offering promising prognostic and therapeutic targets for CRC management.
期刊介绍：
The International Journal of Biological Sciences is a peer-reviewed, open-access scientific journal published by Ivyspring International Publisher. It dedicates itself to publishing original articles, reviews, and short research communications across all domains of biological sciences.
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