Data from TFAP4 Activates &lt;i&gt;IGF2BP1&lt;/i&gt; and Promotes Progression of Non–Small Cell Lung Cancer by Stabilizing &lt;i&gt;TK1&lt;/i&gt; Expression through m6A Modification

Guanghao Sun,Haoyou Wang,Lin Zhang,Qiming Shen,Zhe Xu

doi:10.1158/1541-7786.c.6545640.v1

Abstract

<div>AbstractNon–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.Implications: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.</div>

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