DNA-methylation-mediated silencing of lncRNA PP7080 promotes the progression of gastric cancer by regulating ANKRD1 expression
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.
Authors
- Junying Xu (ORCID: https://orcid.org/0000-0001-6400-0606)
- Xi Wu (ORCID: https://orcid.org/0000-0002-6180-741X)
- Huning Jiang
- Yanmin Zhu (ORCID: https://orcid.org/0000-0002-3968-5372)
- Huiyu Wang (ORCID: https://orcid.org/0000-0003-4984-6616)
- Rui Hou (ORCID: https://orcid.org/0000-0002-6950-2290)
- Kun Ding (ORCID: https://orcid.org/0000-0002-8677-5186)
- Junli Ding
Institutions
- Xuzhou Medical College (CN)
- Wuxi People's Hospital (CN)
- Nanjing Medical University (CN)
Publication Details
- Journal
- Translational Oncology
- Published
- 2025-06-13
- DOI
- https://doi.org/10.1016/j.tranon.2025.102440
- Primary Topic
- Cancer-related molecular mechanisms research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Wuxi Science and Technology Association
- National Natural Science Foundation of China
- Wuxi Health and Family Planning Commission