<br>IGF2BP1通过降低MYC对胃癌的抑癌作用,Cancer Science

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IGF2BP1通过降低MYC对胃癌的抑癌作用
Cancer Science ( IF 4.5 ) Pub Date : 2023-12-19 , 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}

Affiliation

胃癌是全世界癌症相关死亡的最常见原因之一。据报道，N ^{6 -}甲基腺苷 (m ⁶ A) 读取器 IGF2BP1（胰岛素样生长因子-2 mRNA 结合蛋白 1）可通过其在某些肿瘤中的 m ⁶ A 结合活性来稳定致癌 mRNA，从而促进癌症进展。然而，IGF2BP1在胃癌发生中的作用仍不清楚。在这项研究中，我们发现IGF2BP1在胃癌患者的肿瘤组织中显着下调。 IGF2BP1 的低表达与不良预后相关。 IGF2BP1 以 m ⁶ A 依赖性方式抑制胃癌细胞增殖。此外，IGF2BP1 能够显着减弱胃癌细胞的肿瘤生长。进一步的m ⁶ A测序和m ⁶ A-RNA免疫沉淀分析表明， MYC （c-myc原癌基因）mRNA是胃癌细胞中IGF2BP1的靶转录物。 IGF2BP1通过降低MYC mRNA和蛋白表达来抑制胃癌细胞增殖。从机制上讲，IGF2BP1 促进MYC mRNA 的降解并抑制其翻译效率。综上所述，这些数据表明IGF2BP1通过以m ⁶ A依赖性方式下调MYC而在胃癌发生中发挥肿瘤抑制作用，从而使IGF2BP1 -MYC轴成为胃癌治疗的潜在靶点。

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Tumor suppressive function of IGF2BP1 in gastric cancer through decreasing MYC

Gastric cancer is one of the most common causes of cancer-related death worldwide. The N⁶-methyladenosine (m⁶A) reader IGF2BP1 (insulin-like growth factor-2 mRNA binding protein 1) has been reported to promote cancer progression by stabilizing oncogenic mRNAs through its m⁶A-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 m⁶A-dependent manner. Additionally, IGF2BP1 is able to significantly attenuate tumor growth of gastric cancer cells. Further m⁶A sequencing and m⁶A-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 m⁶A-dependent manner, thereby making the IGF2BP1-MYC axis a potential target for gastric cancer treatment.

更新日期：2023-12-19

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