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DNA甲基化介导的lncRNA PP7080沉默通过调节ANKRD1表达促进胃癌进展。

DNA-methylation-mediated silencing of lncRNA PP7080 promotes the progression of gastric cancer by regulating ANKRD1 expression.

作者信息

Jiang Huning, Hou Rui, Wu Xi, Ding Kun, Zhu Yiyao, Wang Huiyu, Ding Junli, Xu Junying

机构信息

Department of Oncology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi 214023, Jiangsu, China.

School of Public Health, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China; Key Laboratory of Human Genetics and Environmental Medicine, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.

出版信息

Transl Oncol. 2025 Jun 13;59:102440. doi: 10.1016/j.tranon.2025.102440.

Abstract

Gastric cancer (GC) is a major public health issue due to its high morbidity and mortality rates. The role of long noncoding RNAs (lncRNAs) in GC progression has received extensive attention. However, the underlying mechanisms by which lncRNAs mediates GC development remain poorly characterized. Through the analysis of database and the detection of GC tissue samples, we found that the expression of lncRNA PP7080 was significantly downregulated in GC. Moreover, an abnormally high level of DNA methylation was detected within the promoter region of lncRNA PP7080 in GC by bioinformatics analysis and bisulfite sequencing. Functional experiments indicated that overexpression of PP7080 inhibited GC cell proliferation and migration, induced cell apoptosis and decreased tumorigenicity in nude mice. Further RNA sequencing revealed that ankyrin repeat protein 1 (ANKRD1) was the crucial target of PP7080. Mechanistically, PP7080 executed its functions via promoting ubiquitination of EZH2 and sponging miR-3614-5p to regulate the downstream target gene ANKRD1. Taken together, these findings suggest that PP7080 is a novel and effective biomarker for GC therapy and may facilitate the development of lncRNA-directed diagnostics and therapeutics against GC.

摘要

胃癌(GC)因其高发病率和死亡率而成为一个重大的公共卫生问题。长链非编码RNA(lncRNAs)在胃癌进展中的作用受到了广泛关注。然而,lncRNAs介导胃癌发展的潜在机制仍不清楚。通过数据库分析和胃癌组织样本检测,我们发现lncRNA PP7080在胃癌中的表达显著下调。此外,通过生物信息学分析和亚硫酸氢盐测序,在胃癌中检测到lncRNA PP7080启动子区域存在异常高水平的DNA甲基化。功能实验表明,PP7080的过表达抑制了胃癌细胞的增殖和迁移,诱导了细胞凋亡,并降低了裸鼠的致瘤性。进一步的RNA测序显示,锚蛋白重复蛋白1(ANKRD1)是PP7080的关键靶点。机制上,PP7080通过促进EZH2的泛素化和吸附miR-3614-5p来调节下游靶基因ANKRD1,从而发挥其功能。综上所述,这些发现表明PP7080是一种新型有效的胃癌治疗生物标志物,可能有助于开发针对胃癌的lncRNA导向诊断和治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/790a/12206047/76741498b793/gr1.jpg

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