DDX5 通过维持 VAV3 mRNA 的稳定性促进食管鳞癌细胞生长。
DDX5 promotes esophageal squamous cell carcinoma growth through sustaining VAV3 mRNA stability.
机构信息
The Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
Tianjian Laboratory for Advanced Biomedical Sciences, Zhengzhou, Henan, China.
出版信息
Oncogene. 2024 Oct;43(44):3240-3254. doi: 10.1038/s41388-024-03162-6. Epub 2024 Sep 17.
Novel therapeutic targets and their inhibitors for esophageal squamous cell carcinoma (ESCC) prevention and therapy are urgently needed. This study aimed to investigate the function of DEAD-box helicase 5 (DDX5) in ESCC progression and to identify a promising inhibitor of DDX5. We verified that DDX5 was highly expressed in ESCC and played an oncogenic role, binding with vav guanine nucleotide exchange factor 3 (VAV3) mRNA and facilitating VAV3 mRNA N6-methyladenosine (m6A) modification by interacting with the m6A methyltransferase 3 (METTL3). M6A-modified VAV3 mRNA was identified by insulin-like growth factor 1 (IGF2BP1), increasing mRNA stability. Methylnissolin-3-β-D-O-glucoside (MD) inhibited ESCC progression through the DDX5-VAV3 axis. Our findings suggest that DDX5 promotes ESCC progression. MD inhibits ESCC progression by targeting DDX5.
需要寻找新的治疗靶点及其抑制剂，用于预防和治疗食管鳞状细胞癌（ESCC）。本研究旨在探究 DEAD-box 解旋酶 5（DDX5）在 ESCC 进展中的作用，并确定 DDX5 的一种有前途的抑制剂。我们验证了 DDX5 在 ESCC 中高度表达，并发挥致癌作用，与 vav 鸟嘌呤核苷酸交换因子 3（VAV3）mRNA 结合，并通过与 m6A 甲基转移酶 3（METTL3）相互作用促进 VAV3 mRNA N6-甲基腺苷（m6A）修饰。胰岛素样生长因子 1（IGF2BP1）识别 m6A 修饰的 VAV3 mRNA，增加 mRNA 稳定性。Methylnissolin-3-β-D-O-glucoside（MD）通过 DDX5-VAV3 轴抑制 ESCC 进展。我们的研究结果表明，DDX5 促进 ESCC 进展。MD 通过靶向 DDX5 抑制 ESCC 进展。
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