{"title":"Gut microbiota protect against colorectal tumorigenesis through lncRNA Snhg9","authors":"Meng Wang, Kailin Liu, Wu Bao, Bingqing Hang, Xianjiong Chen, Xinyi Zhu, Guifang Li, Lihong Liu, Haoyi Xiang, Hai Hu, Yanhui Lu, Zhangfa Song, Jiaxin Chen, Yuhao Wang","doi":"10.1016/j.devcel.2024.12.013","DOIUrl":null,"url":null,"abstract":"The intestinal microbiota is a key environmental factor in the development of colorectal cancer (CRC). Here, we report that, in the context of mild colonic inflammation, the microbiota protects against colorectal tumorigenesis in mice. This protection is achieved by microbial suppression of the long non-coding RNA (lncRNA) <em>Snhg9</em>. <em>Snhg9</em> promotes tumor growth through inhibition of the tumor suppressor p53. <em>Snhg9</em> suppresses p53 activity by dissociating the p53 deacetylase sirtuin 1 (SIRT1) from the cell cycle and apoptosis regulator 2 (CCAR2). Consequently, the depletion of the microbiota by antibiotics causes upregulation of <em>Snhg9</em> and accelerates CRC progression. Moreover, <em>Snhg9</em> is functionally conserved. Human <em>SNHG9</em> promotes tumor growth via the same mechanism as mouse <em>Snhg9</em>, despite their low sequence similarity.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"155 1","pages":""},"PeriodicalIF":10.7000,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Developmental cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.devcel.2024.12.013","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The intestinal microbiota is a key environmental factor in the development of colorectal cancer (CRC). Here, we report that, in the context of mild colonic inflammation, the microbiota protects against colorectal tumorigenesis in mice. This protection is achieved by microbial suppression of the long non-coding RNA (lncRNA) Snhg9. Snhg9 promotes tumor growth through inhibition of the tumor suppressor p53. Snhg9 suppresses p53 activity by dissociating the p53 deacetylase sirtuin 1 (SIRT1) from the cell cycle and apoptosis regulator 2 (CCAR2). Consequently, the depletion of the microbiota by antibiotics causes upregulation of Snhg9 and accelerates CRC progression. Moreover, Snhg9 is functionally conserved. Human SNHG9 promotes tumor growth via the same mechanism as mouse Snhg9, despite their low sequence similarity.
期刊介绍:
Developmental Cell, established in 2001, is a comprehensive journal that explores a wide range of topics in cell and developmental biology. Our publication encompasses work across various disciplines within biology, with a particular emphasis on investigating the intersections between cell biology, developmental biology, and other related fields. Our primary objective is to present research conducted through a cell biological perspective, addressing the essential mechanisms governing cell function, cellular interactions, and responses to the environment. Moreover, we focus on understanding the collective behavior of cells, culminating in the formation of tissues, organs, and whole organisms, while also investigating the consequences of any malfunctions in these intricate processes.