中国药理学通报2024，Vol.40Issue(8)：1462-1473,12.DOI:10.12360/CPB202401068
RNA结合蛋白QKI可通过调节EMT相关基因转录物的切割形成circRNA促进胃癌的发生发展
The RNA binding protein QKI can promote gastric cancer by regulating cleavage of EMT-related gene transcripts to form circRNAs
摘要
Abstract
Aim To study the proliferation,invasion and migration ability of Quaking(QKI)in gastric cancer(GC)via elucidating the molecular mechanisms associated with QKI in the occurrence and development of GC through bioinformatics.Methods Differential expression analysis of QKI was performed across vari-ous human cancer samples by merging data from the TCGA and GTEx databases.The correlation was ana-lyzed between QKI protein expression and tumor muta-tion burden(TMB)score,microsatellite instability(MSI)score,and ESTIMATE score,and the correla-tion was also explored between QKI protein expression and overall survival(OS),disease free survival(DFS),and progression free survival(PFS).EMT related genes that could encode DECircRNAs were ob-tained through bioinformatics analysis to construct a QKI-EMT-circRNAs regulatory network.The differenti-ally expressed circRNAs and EMT related genes in TMK1 cells were verified.The proliferation,invasion and migration ability of the QKI was studied by using the knockdown system.Results QKI was differential-ly expressed in the vast majority of tumors and was closely related to TMB,MSI,and tumor microenviron-ment(TME);QKI emerged as a high-risk factor for predicting OS,DFS,and PFS in individuals with com-mon human cancers.QKI regulated the splicing of 6 EMT related gene transcripts to form eight circRNAs,all of which were significantly associated with the prog-nosis of gastric cancer patients.Cell experiments showed that compared to normal gastric epithelial cells,only hsa_ccirc_0004015,CALD1,and CDK14 were down-regulated in TMK1 cells.Knocking down QKI inhibited the proliferation,invasion and migration ability of TMK1 cells.Conclusion QKI exerts regu-latory control over the transcription of six EMT-related genes,resulting in the formation of circRNAs,thereby promoting the pathogenesis and progression of GC.QKI is highly expressed in TMK1 cells,and knock-down of QKI can inhibit the proliferation,invasion and migration ability of TMK1 cells.关键词
胃癌/QKI/RNA结合蛋白/上皮间充质转化/cir-cRNA/生物信息学分析Key words
gastric cancer/QKI/RNA-binding pro-tein/epithelial-mesenchymal transformation/cir-cRNA/bioinformatics analysis分类
医药卫生引用本文复制引用
崔逸爽,郑璇,吴亚男,么艺涵,王珺,刘子情,孙国贵..RNA结合蛋白QKI可通过调节EMT相关基因转录物的切割形成circRNA促进胃癌的发生发展[J].中国药理学通报,2024,40(8):1462-1473,12.基金项目
国家自然科学基金面上项目(No 82172658) （No 82172658）
唐山市小细胞肺癌医工融合精准诊疗基础创新团队(No 21130203D) （No 21130203D）
华北理工大学公共卫生学院高水平科研创新团队建设计划(No KYTD202309) （No KYTD202309）
