SPDEF suppresses head and neck squamous cell carcinoma progression by transcriptionally activating NR4A1

作     者：Yanting Wang Xianyue Ren Weiyu Li Ruoyan Cao Suyang Liu Laibo Jiang Bin Cheng Juan Xia Yanting Wang;Xianyue Ren;Weiyu Li;Ruoyan Cao;Suyang Liu;Laibo Jiang;Bin Cheng;Juan Xia

作者机构：Hospital of StomatologySun Yat-sen UniversityGuangzhouChina Guangdong Provincial Key Laboratory of StomatologyGuangzhouChina Guanghua School of StomatologySun Yat-sen UniversityGuangzhouChina 

出 版 物：《International Journal of Oral Science》 (国际口腔科学杂志（英文版）)

年 卷 期：2021年第13卷第4期

页      面：370-380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：This work was supported by grants from the National Natural Science Foundation of China(81870769,81702700) the Guangdong Financial Fund for High-Caliber Hospital Construction(174-2018-XMZC-0001-03-0125/D-05,174-2018-XMZC-0001-03-0125/C-08) the Natural Science Foundation of Guangdong Province(2019A1515010679) the Fundamental Research Funds for the Central Universities(19ykpy83) 

主　　题：inhibited SPD NR4A1 

摘      要：SAM pointed domain containing E26 transformation-specific transcription factor(SPDEF)plays dual roles in the initiation and development of human ***,the biological role of SPDEF in head and neck squamous cell carcinoma(HNSCC)remains *** this study,the expression level of SPDEF and its correlation with the clinical parameters of patients with HNSCC were determined using TCGA-HNSC,GSE65858,and our own clinical ***8,colony formation,cell cycle analysis,and a xenograft tumor growth model were used to determine the molecular functions of SPDEF in ***-qPCR,dual luciferase reporter assay,and rescue experiments were conducted to explore the potential molecular mechanism of SPDEF in *** with normal epithelial tissues,SPDEF was significantly downregulated in HNSCC *** with HNSCC with low SPDEF mRNA levels exhibited poor clinical *** SPDEF inhibited HNSCC cell viability and colony formation and induced G0/G1 cell cycle arrest,while silencing SPDEF promoted cell proliferation in *** xenograft tumor growth model showed that tumors with SPDEF overexpression had slower growth rates,smaller volumes,and lower *** could directly bind to the promoter region of NR4A1 and promoted its transcription,inducing the suppression of AKT,MAPK,and NF-κB signaling ***,silencing NR4A1 blocked the suppressive effect of SPDEF in HNSCC ***,we demonstrate that SPDEF acts as a tumor suppressor by transcriptionally activating NR4A1 in *** findings provide novel insights into the molecular mechanism of SPDEF in tumorigenesis and a novel potential therapeutic target for HNSCC.