2. Academic Validation
  3. Tumor suppressive function of IGF2BP1 in gastric cancer through decreasing MYC

Tumor suppressive function of IGF2BP1 in gastric cancer through decreasing MYC

  • Cancer Sci. 2023 Dec 19. doi: 10.1111/cas.16047.
Ning Ding 1 2 3,  Guodong Cao 4,  Zhuo Wang 1 2 3,  Shengjun Xu 5 6,  Wenwen Chen 1 2 3
Affiliations

Affiliations

  • 1 Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
  • 2 Zhejiang University Cancer Center, Hangzhou, China.
  • 3 Institution of Gastroenterology, Zhejiang University, Hangzhou, China.
  • 4 Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, China.
  • 5 Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou, China.
  • 6 Department of Hepatobiliary and Pancreatic Surgery, Hangzhou First People's Hospital, Hangzhou, China.
PMID: 38115228 DOI: 10.1111/cas.16047
Abstract

Gastric Cancer is one of the most common causes of cancer-related death worldwide. The N6 -methyladenosine (m6 A) reader IGF2BP1 (insulin-like growth factor-2 mRNA binding protein 1) has been reported to promote Cancer progression by stabilizing oncogenic mRNAs through its m6 A-binding activity in some tumors. However, the role of IGF2BP1 in gastric carcinogenesis remains unclear. In this study, we found that IGF2BP1 is significantly downregulated in tumor tissues from patients with gastric Cancer. Lower expression of IGF2BP1 is associated with poor prognosis. Gastric Cancer cell proliferation is suppressed by IGF2BP1 in an m6 A-dependent manner. Additionally, IGF2BP1 is able to significantly attenuate tumor growth of gastric Cancer cells. Further m6 A Sequencing and m6 A-RNA immunoprecipitation assays show that MYC (c-Myc proto-oncogene) mRNA is a target transcript of IGF2BP1 in gastric Cancer cells. IGF2BP1 inhibits gastric Cancer cell proliferation by reducing the mRNA and protein expression of MYC. Mechanistically, IGF2BP1 promotes the degradation of MYC mRNA and inhibits its translation efficiency. Taken together, these data suggest that IGF2BP1 plays a tumor-suppressive role in gastric carcinogenesis by downregulating MYC in an m6 A-dependent manner, thereby making the IGF2BP1-MYC axis a potential target for gastric Cancer treatment.

Keywords

IGF2BP1; MYC; RNA metabolism; gastric cancer; m6A.

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