Endometrial cancer,one of the most prevalent gynecological malignancies,has been steadily increasing in incidence,with 417,000 new cases and 97,000 deaths reported worldwide in 2020.1 Its classification is crucial for...Endometrial cancer,one of the most prevalent gynecological malignancies,has been steadily increasing in incidence,with 417,000 new cases and 97,000 deaths reported worldwide in 2020.1 Its classification is crucial for effective management.展开更多
目的探究miR-92a-3p靶向双特异性蛋白磷酸酶1(dual-specificity protein phosphatase 1,DUSP1)在子宫内膜癌(uterine corpus endometrial carcinoma,UCEC)发生发展过程中的功能及内在分子机制。方法运用生物信息学分析策略,从数据库中...目的探究miR-92a-3p靶向双特异性蛋白磷酸酶1(dual-specificity protein phosphatase 1,DUSP1)在子宫内膜癌(uterine corpus endometrial carcinoma,UCEC)发生发展过程中的功能及内在分子机制。方法运用生物信息学分析策略,从数据库中筛选鉴定出miR-92a-3p在UCEC组织及细胞系中存在显著差异的表达模式,并预测其潜在的靶基因。将人工合成的miR-92a-3p模拟物及其对应的阴性对照转染至人UCEC细胞系Ishikawa细胞及HEC-1A细胞,采用Cell Counting Kit-8(CCK-8)法精确测定各组细胞的增殖活性变化;利用Transwell小室实验评估细胞的迁移和侵袭能力;通过实时荧光定量逆转录聚合酶链反应(qRT-PCR)、Western blotting以及双荧光素酶报告基因检测系统,系统阐释miR-92a-3p对DUSP1的基因表达调控关系。构建DUSP1过表达载体并转染至UCEC细胞,借助脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)以及透射电子显微镜技术,观察UCEC细胞的凋亡形态学特征及凋亡相关指标变化。结果生物信息学分析结果显示,在UCEC组织中miR-92a-3p呈现低表达状态,且经预测及后续实验证实DUSP1为miR-92a-3p的直接作用靶点。功能学实验结果表明,miR-92a-3p的过表达能够抑制Ishikawa细胞及HEC-1A细胞的增殖活力,有效减弱细胞的迁移和侵袭潜能。qRT-PCR、Western blotting和双荧光素酶报告基因实验结果共同表明,DUSP1的表达受到miR-92a-3p的负向调控。此外,在UCEC细胞中过表达DUSP1可诱导细胞发生凋亡,呈现出典型的凋亡形态学特征。结论miR-92a-3p可能通过抑制其靶基因DUSP1的转录和翻译过程,进而影响细胞的增殖、迁移、侵袭和凋亡等生物学行为,在UCEC的恶性进展过程中可能发挥重要作用。展开更多
基金sponsored in part by the Natural Science Foundation of Guangxi,China(No.2023GXNSFAA026276)the National Natural Science Foundation of China(No.82072892)+1 种基金the Key Discipline Construction Project of Jiading District Health System(Shanghai,China)(No.XK202405)the Research Innovation Project of Jiading Branch of Shanghai General Hospital,China(No.2025-KJPD-01).
文摘Endometrial cancer,one of the most prevalent gynecological malignancies,has been steadily increasing in incidence,with 417,000 new cases and 97,000 deaths reported worldwide in 2020.1 Its classification is crucial for effective management.
