MAFB-mediated CEBPA regulated human urothelium growth through Wnt/β-catenin signaling pathway  

作　　者：Zhenmin Liu Xingguo Luo Zhicheng Zhang Qiang Zhang Chong Wang Hongsong Chen Chunlan Long Xing Liu Guanghui Wei 

机构地区：[1]Department of Urology,Children’s Hospital of Chongqing Medical University,National Clinical Research Center for Child Health and Disorders,Ministry of Education Key Laboratory of Child Development and Disorders,Chongqing 400014,China [2]Chongqing Key Laboratory of Structural Birth Defect and Reconstruction,Chongqing 400014,China

出　　处：《Genes & Diseases》2025年第1期341-354,共14页基因与疾病(英文)

基　　金：financed by the National Natural Science Foundation of China(No.81970571);the Natural Science Foundation of Chongqing Municipality,China(No.CSTB2022NSCQ-MSX1001);the Program for Youth Innovation in Future Medicine,Chongqing Medical University(No.W0109).

摘　　要：MAFB is essential for regulating male-type urethral differentiation,and especially,its variation can contribute to hypospadias in mice.However,the potential mechanism is still unclear.Here we observed that the basic leucine zipper(bZIP)transcription factor MAFB and CCAAT/enhancer-binding protein alpha(CEBPA)could promote human urothelium SV-HUC-1 growth.Moreover,MAFB and CEBPA expression were reduced in the prepuce tissues of hypospadias patients.Based on transcriptome sequencing analysis and Western blot,MAFB knockdown was found to suppress CEBPA protein expression and repress Wnt/β-catenin signaling in urothelium cells.Meanwhile,we observed blocked cell-cycle progression from the G1 to the S phase,inhibited cell proliferation,and activated apoptosis.Furthermore,MAFB could facilitate CEBPA transcription and regulate the proliferation of urothelium.The above results indicated that MAFB-mediated inhibition of urothelial SV-HUC-1 growth resulted from inhibiting the Wnt/β-catenin signaling pathway by down-regulating CEBPA.Our findings provide new insight into the understanding of genes associated with hypospadias and the pathogenic mechanism of this disorder.

关 键 词：APOPTOSIS CEBPA Cell cycle MAFB UROTHELIUM Wnt/β-catenin signaling pathway 

分 类 号：R73[医药卫生—肿瘤]