2. Academic Validation
  3. N6-methyladenosine modification of REG1α facilitates colorectal cancer progression via β-catenin/MYC/LDHA axis mediated glycolytic reprogramming

N6-methyladenosine modification of REG1α facilitates colorectal cancer progression via β-catenin/MYC/LDHA axis mediated glycolytic reprogramming

  • Cell Death Dis. 2023 Aug 25;14(8):557. doi: 10.1038/s41419-023-06067-6.
Mingxia Zhou # 1,  Jing He # 2,  Yingxia Li 1,  Libin Jiang 1,  Jiaxuan Ran 1,  Chang Wang 3,  Chenxi Ju 3,  Dan Du 3,  Xinyu Xu 3,  Xuexin Wang 1,  Hongle Li 4,  Fucheng He 5,  Hongtao Wen 6
Affiliations

Affiliations

  • 1 Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
  • 2 Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
  • 3 Department of Medical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
  • 4 Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China. [email protected].
  • 5 Department of Medical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. [email protected].
  • 6 Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. [email protected].
  • # Contributed equally.
PMID: 37626036 DOI: 10.1038/s41419-023-06067-6
Abstract

Aerobic glycolysis has been considered as a hallmark of colorectal Cancer (CRC). However, the potential functional regulators of glycolysis in CRC remains to be elucidated. In the current study, we found that Regenerating islet-derived protein 1-alpha (REG1α) was significantly increased in both CRC tissues and serum, and positively associated with CRC patients' lymph node metastasis, advanced tumor stage, and unfavorable prognosis. Ectopic expression of REG1α contributed to various tumorigenic properties, including cell proliferation, cell cycle, migration, invasion, and glycolysis. In contrast, REG1α deficiency in CRC cells attenuated malignant properties and glucose metabolism. Mechanically, REG1α promoted CRC proliferation and metastasis via β-catenin/MYC axis-mediated glycolysis upregulation. Moreover, the malignant behaviors governed by REG1α could be effectively abolished by silencing of Wnt/β-catenin/MYC axis or glycolysis process using specific inhibitors. Besides, REG1α expression was mediated by METTL3 in an m6A-dependent manner. Overall, our work defines a novel regulatory model of the METTL3/REG1α/β-catenin/MYC axis in CRC, which indicates that REG1α could function as a novel biomarker and a potential therapeutic target for patients with CRC.

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