上海交通大学学报（医学版）2025，Vol.45Issue(10)：1288-1297,10.DOI:10.3969/j.issn.1674-8115.2025.10.004
OGT通过ERK信号通路促进非小细胞肺癌增殖的机制研究
Mechanistic study of OGT-promoted non-small cell lung cancer proliferation via the ERK signaling pathway
摘要
Abstract
Objective·To investigate the expression level of O-GlcNAc transferase(OGT)in non-small cell lung cancer(NSCLC)and its impact on lung cancer proliferation,as well as to explore the underlying mechanisms.Methods·The expression of OGT in NSCLC tumors and adjacent normal tissues was detected by immunohistochemistry(IHC).The dataset(GSE31210)from the GEO database was analyzed to assess the correlation between OGT expression and NSCLC patient prognosis.siRNA transfection was performed to knock down OGT expression in H460 and H1299 cells,followed by total RNA extraction and transcriptome sequencing.Pathway enrichment analysis was conducted on differentially downregulated genes in the knockdown group compared with the control group,and Western blotting was used to validate the enrichment results.The effects of OGT knockdown on cell proliferation and colony formation in H460 and H1299 cells were evaluated using the cell counting kit-8(CCK-8)assay and colony formation assay,respectively.The impact of overexpressing downstream genes was also examined.Stable OGT-knockdown cell lines were generated using shRNA and subcutaneously inoculated into nude mice to monitor tumor growth.Results·IHC revealed that OGT expression was significantly upregulated in NSCLC tumor tissues compared to adjacent normal tissues.Patients with high OGT expression exhibited shorter survival times and poorer prognoses than those with low expression.Transcriptome sequencing demonstrated that genes downregulated after OGT knockdown were primarily enriched in the mitogen-activated protein kinase(MAPK)signaling pathway.Western blotting showed that total extracellular regulated protein kinase 1/2(ERK1/2)levels remained unchanged in H460 and H1299 cells after OGT knockdown,while phosphorylated ERK1/2(p-ERK1/2)and its downstream proto-oncogene JUNB protein were markedly reduced.Suppression of OGT expression attenuated the proliferation rate and colony formation capacity of H460 and H1299 cells,whereas JUNB overexpression rescued the proliferation defects induced by OGT knockdown.Notably,H460 cells with stable OGT knockdown formed significantly smaller tumors in nude mice.Conclusion·OGT is highly expressed in NSCLC and correlates with poor prognosis.Knockdown of OGT inhibits NSCLC cell proliferation and clonogenicity in vitro,and tumor growth in vivo.Mechanistically,OGT appears to promote NSCLC progression by activating the ERK/JUNB signaling axis.关键词
非小细胞肺癌/O-GlcNAc糖基转移酶/细胞外调节蛋白激酶/细胞增殖Key words
non-small cell lung cancer(NSCLC)/O-GlcNAc transferase(OGT)/extracellular regulated protein kinase(ERK)/cell proliferation分类
医药卫生引用本文复制引用
张先洲,杜凤麟,吴雷,任逸喆,赵明娜,娄加陶..OGT通过ERK信号通路促进非小细胞肺癌增殖的机制研究[J].上海交通大学学报（医学版）,2025,45(10):1288-1297,10.基金项目
国家自然科学基金(82273380) （82273380）
上海市2022年度"科技创新行动计划"自然科学基金(22ZR1450200). National Natural Science Foundation of China(82273380) （22ZR1450200）
Natural Science Foundation of Shanghai under the 2022 Shanghai Action Plan for Science,Technology and Innovation(22ZR1450200). （22ZR1450200）
