Role of steroid receptor-associated and regulated protein in tumor progression and progesterone receptor signaling in endometrial cancer  

作　　者：Jie Liu Zhiqi Wang Jingyi Zhou Jiaqi Wang Xiangjun He Jianliu Wang 

机构地区：[1]Department of Obstetrics and Gynecology,Peking University People’s Hospital,Beijing 100044,China [2]Central Laboratory and Institute of Clinical Molecular Biology,Peking University People’s Hospital,Beijing 100044,China

出　　处：《Chinese Medical Journal》2023年第21期2576-2586,共11页中华医学杂志（英文版）

基　　金：supported by grants from the National Key Technology R&D Program of China(Nos.2019YFC1005200 and 2019YFC1005201).

摘　　要：Background:Steroid receptor-associated and regulated protein(SRARP)suppresses tumor progression and modulates steroid receptor signaling by interacting with estrogen receptors and androgen receptors in breast cancer.In endometrial cancer(EC),progesterone receptor(PR)signaling is crucial for responsiveness to progestin therapy.The aim of this study was to investigate the role of SRARP in tumor progression and PR signaling in EC.Methods:Ribonucleic acid sequencing data from the Cancer Genome Atlas,Clinical Proteomic Tumor Analysis Consortium,and Gene Expression Omnibus were used to analyze the clinical significance of SRARP and its correlation with PR expression in EC.The correlation between SRARP and PR expression was validated in EC samples obtained from Peking University People’s Hospital.SRARP function was investigated by lentivirus-mediated overexpression in Ishikawa and HEC-50B cells.Cell Counting Kit-8 assays,cell cycle analyses,wound healing assays,and Transwell assays were used to evaluate cell proliferation,migration,and invasion.Western blotting and quantitative real-time polymerase chain reaction were used to evaluate gene expression.The effects of SRARP on the regulation of PR signaling were determined by co-immunoprecipitation,PR response element(PRE)luciferase reporter assay,and PR downstream gene detection.Results:Higher SRARP expression was significantly associated with better overall survival and disease-free survival and less aggressive EC types.SRARP overexpression suppressed growth,migration,and invasion in EC cells,increased E-cadherin expression,and decreased N-cadherin and Wnt family member 7A(WNT7A)expression.SRARP expression was positively correlated with PR expression in EC tissues.In SRARP-overexpressing cells,PR isoform B(PRB)was upregulated and SRARP bound to PRB.Significant increases in PRE-based luciferase activity and expression levels of PR target genes were observed in response to medroxyprogesterone acetate.Conclusions:This study illustrates that SRARP exerts a tumor-suppressiv

关 键 词：SRARP Progesterone receptor Epithelial-mesenchymal transition COREGULATOR Tumor suppressor Endometrial cancer 

分 类 号：R737.33[医药卫生—肿瘤]