中国耳鼻咽喉头颈外科2025，Vol.32Issue(11)：681-687,7.DOI:10.16066/j.1672-7002.2025.11.001
Krüppel样转录因子7促进头颈鳞状细胞癌疾病进展的作用机制研究
Mechanism study of Krüeppel-Like factor 7 in promoting the progression of head and neck squamous cell carcinoma
摘要
Abstract
OBJECTIVE To explore the mechanism by which Krüppel-like factor 7(KLF7)promotes the disease progression of head and neck squamous cell carcinoma(HNSCC).METHODS In this study,the genes related to HNSCC cell-specific super enhancers(SEs)were identified through H3K27Ac chromatin immunoprecipitation sequencing(ChIP-seq)technology,and the core genes related to HNSCC were screened based on the Cancer Genome Atlas(TCGA)and the Comprehensive Gene Expression(GEO)database.To detect the expression levels of insulin-like growth factor 2-binding protein 2(IGF2BP2)and KLF7 in HNSCC tissues;The biological effects of IGF2BP2 were clarified by using cell counting test-8(CCK-8)assay,colony formation assay and Transwell migration assay.The regulatory mechanism of IGF2BP2 and its upstream transcription factors were evaluated by using small molecule inhibitors and dual-luciferase reporter gene assays.RESULTS 1.The expression levels of IGF2BP2 mRNA in the HNSCC group were significantly higher than those in the normal tissue group(P<0.05).2.Silencing of the IGF2BP2 gene leads to a reduction in the proliferation ability of SCC25 and CAL27 cell lines,with a significant decrease in the number and size of clone colonies formed.In contrast,overexpression of IGF2BP2 results in enhanced cell proliferation ability,increased formation of clone colonies,and enhanced cell migration and invasion abilities(P<0.05).3.After silencing with BRD4 or MED1,the mRNA and protein levels of IGF2BP2 were significantly decreased,and the enrichment of BRD4 or MED1 in the IGF2BP2-SE region was reduced(P<0.05).Treatment with small molecule inhibitors THZ1,JQ1,OTX-015 and CPI-637 could all lead to a significant decrease in the mRNA and protein levels of IGF2BP2(P<0.05).Treatment with JQ1 or CPI-637 can lead to a reduction in the enrichment of histone modification H3K27 on IGF2BP2-SE(P<0.05).4.The results of the correlation analysis showed that the expression levels of KLF7 and IGF2BP2 were positively correlated(P<0.05).The expression of KLF7 mRNA in HNSCC tissues was significantly upregulated compared with that in normal tissues(P<0.05).The expression levels of IGF2BP2 protein and mRNA in SCC25 and CAL27 cells of the KLF7 silencing group were 0.12±0.02,0.23±0.03,0.13±0.03 and 0.24±0.02 respectively,which were lower than that of the blank control group 0.99±0.08,1.01±0.04(P<0.05).The transcription and expression levels of IGF2BP2 in the KLF7 overexpression group were 6.22±0.72 and 3.83±0.53,respectively,which were higher than those in the blank control group(1.00±0.04 and 1.01±0.04)(P<0.05).The results of dual-luciferase plasmid analysis showed that the luciferase activity of wild-type transfected cells significantly increased,while that of mutant transfected cells significantly decreased(P<0.05).CONCLUSION The overexpression of IGF2BP2 mediated by KLF7 plays a key role in the progression of HNSCC disease,and the SEs transcription link may be a potential therapeutic target for HNSCC.关键词
头颈部肿瘤/头颈鳞状细胞癌/胰岛素样生长因子2结合蛋白2/Krüppel样转录因子7Key words
Head and Neck Neoplasms/Squamous Cell Carcinoma of Head and Neck/Insulin-like growth factor 2 binding protein 2/Krüppel-like factor 7引用本文复制引用
宋来小,刘佳荣,李欣,崔晓波,徐海侠..Krüppel样转录因子7促进头颈鳞状细胞癌疾病进展的作用机制研究[J].中国耳鼻咽喉头颈外科,2025,32(11):681-687,7.基金项目
内蒙古自治区自然科学基金(2025SHZR0025) （2025SHZR0025）
