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

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2025-06-13 DOI:10.1016/j.tranon.2025.102440

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

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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.

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dna甲基化介导的lncRNA PP7080沉默通过调节ANKRD1表达促进胃癌的进展

胃癌因其高发病率和高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GC进展中的作用已受到广泛关注。然而，lncRNAs介导GC发育的潜在机制仍然不清楚。通过数据库分析和GC组织样本检测，我们发现lncRNA PP7080在GC中表达明显下调。此外，通过生物信息学分析和亚硫酸盐测序，在GC中lncRNA PP7080的启动子区域检测到异常高水平的DNA甲基化。功能实验表明，过表达PP7080可抑制胃癌细胞的增殖和迁移，诱导细胞凋亡，降低裸鼠的致瘤性。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。在机制上，PP7080通过促进EZH2泛素化和海绵miR-3614-5p调节下游靶基因ANKRD1来发挥其功能。综上所述，这些发现表明PP7080是一种新的有效的GC治疗生物标志物，并可能促进lncrna导向的GC诊断和治疗方法的发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.