Gut microbiota protect against colorectal tumorigenesis through lncRNA Snhg9

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

Gut microbiota protect against colorectal tumorigenesis through lncRNA Snhg9

Dev Cell. 2024 Dec 24:S1534-5807(24)00734-2. doi: 10.1016/j.devcel.2024.12.013. Online ahead of print.

Authors

Meng Wang¹, Kailin Liu¹, Wu Bao¹, Bingqing Hang¹, Xianjiong Chen¹, Xinyi Zhu¹, Guifang Li¹, Lihong Liu², Haoyi Xiang³, Hai Hu⁴, Yanhui Lu⁵, Zhangfa Song⁶, Jiaxin Chen⁷, Yuhao Wang⁸

Affiliations

¹ Zhejiang Provincial Key Laboratory of Pancreatic Disease of The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou 310029, Zhejiang, China.
² Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China.
³ Department of Colorectal Surgery and Key Laboratory of Biotherapy of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, Zhejiang, China.
⁴ Breast Cancer Center, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310022, Zhejiang, China.
⁵ School of Nursing, Peking University, Beijing 100191, China.
⁶ Department of Colorectal Surgery and Key Laboratory of Biotherapy of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, Zhejiang, China. Electronic address: songzhangfa@zju.edu.cn.
⁷ Department of Breast Surgery and Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China. Electronic address: jiaxinchen@zju.edu.cn.
⁸ Zhejiang Provincial Key Laboratory of Pancreatic Disease of The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou 310029, Zhejiang, China; Cancer Center, Zhejiang University, Hangzhou 310029, Zhejiang, China; Institute of Fundamental and Transdisciplinary Research, Zhejiang University, Hangzhou 310029, Zhejiang, China. Electronic address: yuhaowang@zju.edu.cn.

PMID: 39755115
DOI: 10.1016/j.devcel.2024.12.013

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.

Keywords: Snhg9; colorectal cancer; lncRNA; microbiota.