Results: Our study identified IGF2BP2 as a hub SE-associated gene that exhibited aberrant expression in HNSCC tissues. Increased expression of IGF2BP2 was observed to be linked with malignant progression and unfavorable prognosis in HNSCC patients. Both in vitro and in vivo experiments confirmed that IGF2BP2 promotes the tumorigenicity and metastasis of HNSCC by promoting cell proliferation, migration, and invasion. Mechanistically, the IGF2BP2-SE region displayed enrichment for H3K27Ac, BRD4, and MED1, which led to the inhibition of IGF2BP2 transcription and expression through deactivation of the SE-associated transcriptional program. Additionally, KLF7 was found to induce the transcription of IGF2BP2 and directly bind to its promoter and SE regions. Moreover, the abundance of KLF7 exhibited a positive correlation with the abundance of IGF2BP2 in HNSCC. Patients with high expression of both KLF7 and IGF2BP2 showed poorer prognosis. Lastly, we demonstrated that the small molecule inhibitor JQ1, targeting BRD4, attenuated the proliferation and metastatic abilities of HNSCC cells.
Conclusions: Our study reveals the critical role of IGF2BP2 overexpression mediated by SE and KLF7 in promoting HNSCC progression. Targeting SE-associated transcriptional programs may represent a potential therapeutic strategy in managing HNSCC.
Congratulations to Professors Cheng Wang and Jinsong Hou from Sun Yat-Sen University (Guangzhou, China) for their excellent work published in J Exp Clin Cancer Res (IF=12.7)!
InvivoChem is proud to provide Professors Cheng Wang and Jinsong Hou with our high-quality product THZ1 (Cat#: V2557, CDK7 inhibitor) and (+)-JQ1 (Cat#: V0411, BET inhibitor) for this research.
References: J Exp Clin Cancer Res. 2024 Mar 5;43(1):69. doi: 10.1186/s13046-024-02996-y.
