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第43卷第11期                           南京医科大学学报(自然科学版)
                 2023年11月                   Journal of Nanjing Medical University(Natural Sciences)     ·1487 ·


               ·基础研究·

                转录因子STAT1对癌症相关基因Gas6的调控研究



                颜 凤,邱佳韵,庄丽丽,周国平             *
                南京医科大学第一附属医院儿科,江苏 南京                 210009




               [摘   要] 目的:研究信号转导和转录激活因子1(signal transducer and activator of transcription 1,STAT1)对癌症相关生长抑制
                特异性基因6(growth arrest specific 6,Gas6)的影响及其机制。方法:应用数据库预测乳腺癌的基因聚类分析结果,并预测Gas6
                与 STAT1 在多种癌症中的相关性;通过染色质免疫沉淀(chromatin immunoprecipitation,ChIP)实验检测 STAT1 是否可与 Gas6
                启动子结合,应用数据库预测STAT1在Gas6启动子上的结合位点并突变其关键碱基,通过双萤光素酶报告基因实验检测结合
                位点突变对Gas6启动子活性的影响,同时分别检测敲低或过表达STAT1对Gas6启动子和突变的Gas6启动子活性的影响;通
                过实时荧光定量 PCR 技术和蛋白质免疫印迹技术分别检测敲低或过表达 STAT1 对 Gas6 mRNA 及蛋白表达的影响。结果:
                Gas6基因在乳腺癌中高表达;Gas6与STAT1在多种癌症中有正相关趋势;Gas6启动子序列包含STAT1的结合位点,并且有调
                控Gas6启动子活性的功能性结合位点。转录因子STAT1可在转录水平对癌症相关基因Gas6进行正向调控。结论:癌症相关
                基因Gas6是转录因子STAT1的直接靶基因。
               [关键词] Gas6;STAT1;启动子;转录调控;癌症
               [中图分类号] R730.231                  [文献标志码] A                     [文章编号] 1007⁃4368(2023)11⁃1487⁃07
                doi:10.7655/NYDXBNS20231102


                The regulation of the transcription factor STAT1 to cancer⁃related gene Gas6

                YAN Feng,QIU Jiayun,ZHUANG Lili,ZHOU Guoping  *
                Department of Pediatrics,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210009,China


               [Abstract] Objective:The current study aims to investigate the effect and mechanism of signal transducer and activator of
                transcription 1(STAT1)on cancer⁃related gene Gas6. Methods:The database was used to predict the results of the gene cluster
                analysis of breast cancer,and to predict the correlation between Gas6 and STAT1 in multiple cancers. The binding of STAT1 to Gas6
                promoter was tested by chromatin immunoprecipitation(ChIP)assays. The binding sites of STAT1 on Gas6 promoter were predicted by
                bioinformatics analysis and identified by mutation plasmid construction,and the effects of binding site mutation on activity of Gas6
                promoter was detected by dual luciferase reporter assay. The effects of knockdown and overexpression of STAT1 on Gas6 mRNA and
                protein expression were measured by qRT⁃PCR and Western blot,respectively. Results:Gas6 was a highly expressed gene in breast
                cancer. Gas6 was positively associated with STAT1 in multiple cancers. The Gas6 promoter contained binding sites of STAT1. STAT1
                positively regulateed Gas6 at transcriptional levels. Conclusion:The cancer related gene Gas6 is a direct target gene for transcription
                factor STAT1.
               [Key words] Gas6;STAT1;promoter;transcriptional regulation;cancer
                                                                            [J Nanjing Med Univ,2023,43(11):1487⁃1493]




                    癌症是当前全球广泛关注的健康问题,具有慢                          与癌症发病相关的主要风险因素包括遗传、吸烟、
                性发展和致死倾向两大特征。近年来,癌症的发病                            饮酒、肥胖、不健康的饮食习惯和运动量不足等 。
                                                                                                             [2]
                率和致死率迅速上升,已成为中国最常见的疾病死                            根据 2020 年全球癌症统计数据,乳腺癌已超过肺
                因,在美国是仅次于心脏病的第二大疾病死因 。                            癌,成为世界上最常见的癌症             [3-4] ,同时是女性癌症相
                                                           [1]
               [基金项目] 国家自然科学基金(82270068)                          关死亡的主要原因        [4-6] 。但目前对癌症的治疗,如手
                ∗                                                 术切除、放疗、化疗和靶向治疗,通常需要较长的周
                通信作者(Corresponding author),E⁃mail:guopzhou@126.com
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