Gut microbiota protect against colorectal tumorigenesis through lncRNA Snhg9

IF 10.7 1区 生物学 Q1 CELL BIOLOGY Developmental cell Pub Date : 2025-01-03 DOI:10.1016/j.devcel.2024.12.013
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
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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.

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肠道微生物群通过lncRNA Snhg9保护结肠直肠癌的发生
肠道微生物群是结直肠癌(CRC)发展的关键环境因素。在这里,我们报道,在轻度结肠炎症的背景下,微生物群可以防止小鼠结肠直肠肿瘤的发生。这种保护是通过微生物抑制长链非编码RNA (lncRNA) Snhg9实现的。Snhg9通过抑制肿瘤抑制因子p53促进肿瘤生长。Snhg9通过将p53去乙酰化酶SIRT1 (SIRT1)与细胞周期和凋亡调节因子2 (CCAR2)分离来抑制p53活性。因此,抗生素消耗微生物群导致Snhg9上调并加速结直肠癌的进展。此外,Snhg9在功能上是保守的。人类SNHG9通过与小鼠SNHG9相同的机制促进肿瘤生长,尽管它们的序列相似性较低。
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来源期刊
Developmental cell
Developmental cell 生物-发育生物学
CiteScore
18.90
自引率
1.70%
发文量
203
审稿时长
3-6 weeks
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.
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