Down-regulation of microRNA-23a promotes pancreatic ductal adenocarcinoma initiation and progression by up-regulation of FOXM1 expression

作     者：Lixin Liang Tian Cai Xiaojia Li Jianhong An Sen Yu Yang Zhang Fengjie Guo Fang Wei Jie He Keping Xie Tingting Jiang 

作者机构：Center for Pancreatic Cancer ResearchSouth China University of Technology School of MedicineGuangzhouGuangdong 510006China Department of Laboratory MedicineThe Sixth Affiliated Hospital and Nanhai People’s HospitalSouth China University of Technology School of MedicineFoshanGuangdong 528200China The Second Affiliated Hospital and Guangzhou First People’s HospitalSouth China University of Technology School of MedicineGuangzhouGuangdong 510006China 

出 版 物：《Genes & Diseases》 (基因与疾病（英文）)

年 卷 期：2024年第11卷第5期

页      面：456-469页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：Guangzhou Ruiqian Biotech Company(China)(No.20230330 to TJ) the National Natural Science Foundation of China(No.82072632) Guangzhou Municipality Bureau of Science and Technology,Guangzhou,China(No.202102010033) the Natural Science Foundation of Guangdong Province,China(No.2022A1515012585 to KX) 

主　　题：FOXM1 Gene expression Gene regulation MicroRNA Pancreatic cancer Targeted therapy 

摘      要：Transcriptional factor Forkhead box M1(FOXM1)plays an important role in pancreatic ductal adenocarcinoma(PDAC)development and *** molecular mechanisms underlying its dysregulation remain *** identified and functionally validated the microRNAs(miRNAs)that critically regulate FOXM1 expression in *** expression levels of miRNA-23a(miR-23a-3p and-5p)were altered in PDAC cell lines and their effects on FOXM1 signaling and cell proliferation and migration and tumorigenesis were examined in vitro and in vivo using mouse PDAC *** with non-tumor pancreatic tissues,PDAC tissues and cell lines exhibited significantly reduced levels of miR-23a *** miR-23a expression and concomitant increase in FOXM1 expression were also observed in acinar-toductal metaplasia and pancreatic intraepithelial neoplasia,the major premalignant lesions of *** expression of miR-23a reduced the expression of FOXM1 and suppressed cell proliferation and migration in PDAC cells,whereas the inhibitors of miR-23a did the *** or reduced levels of miR-23a increased the levels of FOXM1 expression,while increased expression of FOXM1 down-regulated miR-23a expression,suggesting that miR-23a and FOXM1 were mutual negative regulators of their expression in PDAC ***,the miR-23a/FOXM1 signaling axis is important in PDAC initiation and progression and could serve as an interventional or therapeutic target for patients with early or late stages of PDAC.