2. Academic Validation
  3. LOH12CR2 activated by sodium butyrate suppresses tumorigenesis in colorectal cancer via METTL14-mediated N6-methyladenosine modification of SPC24 mRNA

LOH12CR2 activated by sodium butyrate suppresses tumorigenesis in colorectal cancer via METTL14-mediated N6-methyladenosine modification of SPC24 mRNA

  • Cell Signal. 2025 Aug 21:136:112079. doi: 10.1016/j.cellsig.2025.112079.
Yanbing Lin 1,  Qianwen Zhou 2,  Mengqi Li 3,  Sucheng Hou 4,  Jia Xu 3,  Dongfang Dai 5,  Xiaoqin Yuan 6
Affiliations

Affiliations

  • 1 Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing 211166, China; Research Center for Environment and Female Reproductive Health, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, China.
  • 2 Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing 211166, China; Department of Gastroenterology, School of Medicine, Zhongda Hospital, Southeast University, Nanjing, China.
  • 3 Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing 211166, China.
  • 4 Nanjing Foreign Language School, Nanjing, China.
  • 5 Department of Radiotherapy, The Affiliated Cancer Hospital of Nanjing Medical University& Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China. Electronic address: ddfszl@njmu.edu.cn.
  • 6 Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing 211166, China. Electronic address: yuanxq@njmu.edu.cn.
PMID: 40848939 DOI: 10.1016/j.cellsig.2025.112079
Abstract

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.

Keywords

CRC; LOH12CR2; METTL14; NaB; SPC24; m6A.

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