南京医科大学学报（自然科学版）2025，Vol.45Issue(9)：1229-1241,13.DOI:10.7655/NYDXBNSN250504
circ_0003633对肺腺癌细胞奥希替尼耐药的作用研究
Role of circ_0003633 in osimertinib resistance in lung adenocarcinoma cells
摘要
Abstract
Objective:To explore the role of circ_0003633 in osimertinib resistance of lung adenocarcinoma cells.Methods:By performing circRNA sequencing on osimertinib-resistant and sensitive cells,circ_0003633 was identified as significantly highly expressed in the resistant cells.The expression of circ_0003633 was knocked down in osimertinib-resistant cells,and its role in osimertinib-resistant lung adenocarcinoma cells was investigated through CCK-8 assay,Transwell assay and colony formation assay.RNA pulldown assay,transcriptome sequencing and bioinformatics analysis were used to screen downstream target genes and signaling pathways.Results:circ_0003633 was significantly highly expressed in osimertinib-resistant cells.Knockdown of circ_0003633 enhanced the sensitivity of resistant cells to osimertinib.circ_0003633 bound to RNA-binding protein hnRNPA1 and regulated the downstream target gene ALDOC to exert its biological functions.Conclusion:circ_0003633 is highly expressed in osimertinib-resistant cells,binds to hnRNPA1,and regulates the downstream target gene ALDOC,thereby activating the PI3K/AKT signaling pathway to promote the resistance of lung adenocarcinoma cells to osimertinib.It may serve as a potential therapeutic target for reversing drug resistance.关键词
肺腺癌/奥希替尼耐药/circRNAKey words
lung adenocarcinoma/osimertinib resistance/circRNA分类
医药卫生引用本文复制引用
张鸽,陈昕,顾婧瑶,王朝霞..circ_0003633对肺腺癌细胞奥希替尼耐药的作用研究[J].南京医科大学学报（自然科学版）,2025,45(9):1229-1241,13.基金项目
国家自然科学基金(82072591) （82072591）
江苏省卫生健康委面上项目(H2023013) （H2023013）
南京医科大学科技发展基金(NMUB20240004) （NMUB20240004）
