Department of Thoracic Surgery, The First Hospital of China Medical University, Heping Area, Shenyang, Liaoning, China.
Mol Cancer Res. 2022 Dec 2;20(12):1763-1775. doi: 10.1158/1541-7786.MCR-22-0231.
Non-small cell lung cancer (NSCLC) is a well-known global health concern. TFAP4 has been reported to function as an oncogene. This study sought to investigate the molecular mechanism of TFAP4 in NSCLC development. Significantly highly-expressed gene IGF2BP1 was screened on online databases and its downstream gene TK1 was predicted. IGF2BP1 promoter sequence was identified. The binding site of TFAP4 and IGF2BP1 was predicted. The expression correlations among TFAP4, IGF2BP1, and TK1 were confirmed. The correlations between TFAP4, IGF2BP1, TK1, and NSCLC prognosis were predicted. NSCLC and paracancerous tissues were collected. The expressions of TFAP4, IGF2BP1, and TK1 were detected. NSCLC cell proliferation, migration, invasion, and apoptosis were detected. The binding of TFAP4 to the IGF2BP1 promoter was verified. m6A modification of TK1 mRNA was detected. The correlation between IGF2BP1 and TK1 was confirmed. A subcutaneous tumor xenograft model was established to validate the effect of TFAP4 in vivo. IGF2BP1 was highly expressed in NSCLC tissues and cells. IGF2BP1 knockdown repressed NSCLC cell proliferation, migration, and invasion and facilitated apoptosis. Mechanically, TFAP4 transcriptionally activated IGF2BP1. IGF2BP1 stabilized TK1 expression via m6A modification and promoted NSCLC cell proliferation, migration, and invasion. In vivo experiments confirmed that TFAP4 knockdown suppressed tumor growth by downregulating IGF2BP1/TK1.
Our findings revealed that TFAP4 activated IGF2BP1 and facilitated NSCLC progression by stabilizing TK1 expression via m6A modification, which offered new insights into the diagnosis and treatment of NSCLC.
非小细胞肺癌（NSCLC）是一个众所周知的全球健康问题。TFAP4 已被报道为一种癌基因。本研究旨在探讨 TFAP4 在 NSCLC 发展中的分子机制。在线数据库筛选出高度表达的基因 IGF2BP1，并预测其下游基因 TK1。鉴定 IGF2BP1 启动子序列。预测 TFAP4 和 IGF2BP1 的结合位点。验证 TFAP4、IGF2BP1 和 TK1 之间的表达相关性。预测 TFAP4、IGF2BP1、TK1 与 NSCLC 预后的相关性。收集 NSCLC 和癌旁组织。检测 TFAP4、IGF2BP1 和 TK1 的表达。检测 NSCLC 细胞增殖、迁移、侵袭和凋亡。验证 TFAP4 与 IGF2BP1 启动子的结合。检测 TK1 mRNA 的 m6A 修饰。验证 IGF2BP1 和 TK1 之间的相关性。建立皮下肿瘤异种移植模型以验证 TFAP4 在体内的作用。IGF2BP1 在 NSCLC 组织和细胞中高表达。IGF2BP1 敲低抑制 NSCLC 细胞增殖、迁移和侵袭，促进凋亡。机制上，TFAP4 转录激活 IGF2BP1。IGF2BP1 通过 m6A 修饰稳定 TK1 表达，促进 NSCLC 细胞增殖、迁移和侵袭。体内实验证实，TFAP4 敲低通过下调 IGF2BP1/TK1 抑制肿瘤生长。
本研究揭示了 TFAP4 通过 m6A 修饰稳定 TK1 表达，激活 IGF2BP1，促进 NSCLC 进展，为 NSCLC 的诊断和治疗提供了新的思路。
