2. Academic Validation
  3. METTL16 Promotes Stability of SYNPO2L mRNA and leading to Cancer Cell Lung Metastasis by Secretion of COL10A1 and attract the Cancer-Associated Fibroblasts

METTL16 Promotes Stability of SYNPO2L mRNA and leading to Cancer Cell Lung Metastasis by Secretion of COL10A1 and attract the Cancer-Associated Fibroblasts

  • Int J Biol Sci. 2024 Aug 1;20(11):4128-4145. doi: 10.7150/ijbs.95375.
Jianlong Wu 1 2 3,  Peng Ouyang 3,  Rui Huang 4,  Yao Cui 5,  Zhihao Yang 6,  Wei Xu 3,  Rui Ma 7,  Guoan Xiang 4,  Wei Zeng 8,  Wang Wu 7 9,  Jian Li 2 10
Affiliations

Affiliations

  • 1 Department of General Surgery, Zhongshan City People's Hospital, Zhongshan, Guangdong 528403, P.R. China.
  • 2 Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou, Henan 450003, P.R. China.
  • 3 Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510632, P.R. China.
  • 4 Department of Gastrointestinal surgery, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong 510317, P.R. China.
  • 5 Department of Oncology, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, P.R. China.
  • 6 Department of Biological Science, Mellon College of Science, Carnegie Mellon University. 5000 Forbes Avenue, Pittsburgh, PA, USA 15213.
  • 7 College of Bioengineering, Chongqing University, Chongqing 400044, P.R. China.
  • 8 Department of General Surgery, Yiyang Central Hospital Affiliated to Hunan University of Chinese Medicine, Yiyang, Hunan 413000, P.R. China.
  • 9 Institute of Burn Research, Third Military Medical University, Chongqing 400038, P.R. China.
  • 10 Department of General Surgery, Henan Cancer Hospital, Zhengzhou, Henan 450003, P.R. China.
PMID: 39247832 DOI: 10.7150/ijbs.95375
Abstract

The occurrence of metastasis is a major factor contributing to poor prognosis in colorectal Cancer. Different stages of the disease play a crucial role in distant metastasis. Furthermore, m6A has been demonstrated to play a significant role in regulating tumor metastasis. Therefore, we conducted an analysis of transcriptome data from high-stage and low-stage colorectal Cancer patients in The Cancer Genome Atlas (TCGA) to identify genes associated with m6A-related regulation. We identified SYNPO2L as a core gene regulated by m6A, and it is correlated with adverse prognosis and metastasis in patients. Additionally, we demonstrated that the m6A writer gene Mettl16 can regulate the stability of SYNPO2L through interaction with YTHDC1. Subsequently, using Weighted Gene Co-expression Network Analysis (WGCNA), we discovered that SYNPO2L can regulate COL10A1, mediating the actions of Cancer-Associated Fibroblasts. SYNPO2L promotes the secretion of COL10A1 and the infiltration of tumor-associated fibroblasts, thereby facilitating Epithelial-Mesenchymal Transition (EMT) in tumor cells and making them more prone to distant metastasis.

Keywords

Cancer-Associated Fibroblasts; Colorectal Cancer; Epithelial-Mesenchymal Transition; Metastasis; N6-methyladenosine.

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