首页|RUNX1通过调节SOX2转录促进食管鳞状细胞癌干性

RUNX1通过调节SOX2转录促进食管鳞状细胞癌干性

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目的:探讨RUNT相关转录因子1(RUNX1)在食管鳞状细胞癌中的表达及其对细胞干性的影响.方法:从GEPIA数据库和GEO数据库(GSE111011)获取RUNX1的表达情况,使用TCGA数据库分析基因表达相关性.利用Western blot检测RUNX1、SOX2、OCT4、KLF4 和 c-MYC 蛋白表达情况.利用 qRT-PCR 技术检测 CD271、CD44、CD54、SOX2 和 RUNX1 的 mRNA水平,双荧光素酶报告基因实验检测SOX2启动子活性.通过细胞成球培养和流式细胞术检测侧群细胞和CD271+/CD44+细胞的数量反映细胞干性.结果:GEPIA数据库、GEO数据库和Western blot结果均显示RUNX1在食管癌中高表达.在Eca-109细胞中敲低RUNX1后,抑制SOX2表达和细胞干性(P<0.01).在KYSE-150细胞中过表达RUNX1后,促进SOX2表达和细胞干性增加(P<0.01).在KYSE-150细胞中同时过表达RUNX1和敲低SOX2后,RUNX1促进的细胞干性增加被逆转(P<0.01).双荧光素酶报告基因实验结果显示RUNX1促进SOX2启动子活性,在转录水平调节SOX2表达.结论:RUNX1在食管鳞状细胞癌中高表达,并通过在转录水平调节SOX2表达,从而促进细胞干性.
RUNX1 promotes stemness by regulating SOX2 transcription in esophageal squamous cell carcinoma
Objective:To investigate the expression of RUNT-related transcription factor 1(RUNX1)and its effect on the cell stemness in esophageal squamous cell carcinoma.Methods:The expression of RUNX1 was generated from GEPIA database and GEO database(GSE111011),and gene expression correlation was analyzed using TCGA database.The protein expression of RUNX1,SOX2,OCT4,KLF4 and c-MYC was detected by Western blot.The mRNA levels of CD271,CD44,CD54,and SOX2 were measured using qRT-PCR,and the promoter activity of SOX2 was determined by dual luciferase reporter gene assay.Cell spheroid culture and flow cytometry were used to detect the number of side population cells and CD271+/CD44+cells reflecting the cell stemness.Results:Thedata from both GEPIA and GEO databases as well as Western blotting results showed that RUNX1 was highly expressed in esophageal cancer.Knockdown of RUNX1 in Eca-109 cells suppressed SOX2 expression and cell stemness(P<0.01),yet overexpression of RUNX1 in KYSE-150 cells promoted SOX2 expression and increased cell stemness(P<0.01).After simultaneous overexpression of RUNX1 and knockdown of SOX2 in KYSE-150 cells,the increase in cell stemness promoted by RUNX1 was reversed(P<0.01).Dual luciferase reporter gene assay demonstrated that RUNX1 could promote SOX2 promoter activity and regulate SOX2 expression at the transcriptional level.Conclusion;RUNX1 is highly expressed in esophageal squamous cell carcinoma and promotes cell stemness by regulating SOX2 expression at the transcriptional level.

RUNT-related transcription factor 1sex-determining region Y-box 2stemnessesophageal squamous cell carcinoma

黄滔、尤琦、Ifeanyi Christian Onyebuchi、朱少金

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皖南医学院第一附属医院弋矶山医院 胸外科,安徽 芜湖 241001

RUNT相关转录因子1 性别决定区Y框蛋白2 干性 食管鳞状细胞癌

安徽省高等学校自然科学研究项目安徽省卫生健康委科研项目皖南医学院大学生科研资助金项目

2023AH040264AHWJ2023BAc10056WK2023XS60

2024

皖南医学院学报
皖南医学院

皖南医学院学报

CSTPCD
影响因子:0.695
ISSN:1002-0217
年,卷(期):2024.43(4)