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CircDYRK1A Suppresses Gastric Cancer Progression via Sponging miR-331-5p to Regulate GADD45A
Shan Chen1, JingFu Liu1, Zhen Li1
1Department of Blood Transfusion, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, NHC Key Laboratory of Cancer Metabolism, Fuzhou, China.
Abstract:
Numerous studies have demonstrated that circRNAs exhibit abnormal expression patterns in cancer and contribute to the regulation of malignant tumor progression. This study aims to investigate the role of circDYRK1A in the progression of Gastric Cancer (GC). Bioinformatics and qRT-PCR analyses revealed significant downregulation of circDYRK1A in GC tissues and cell lines. The circular structure and stability of circDYRK1A were confirmed via Sanger sequencing, electrophoresis, and RNase R treatment. Subcellular localization experiments indicated predominant cytoplasmic distribution. The effects of circDYRK1A on the functions of GC cells were evaluated through CCK-8, EDU proliferation and Transwell assays. The interaction between circDYRK1A and miR-331-5p/GADD45A was validated by dual luciferase assay, RNA immunoprecipitation, western blotting, and rescue assay. The research results showed that circDYRK1A was significantly down-regulated in GC and inhibited the proliferation, migration and invasion of GC cells by the miR-331-5p/GADD45A axis. This study lays a theoretical foundation for the molecular mechanism by which circDYRK1A inhibits the progression of GC and opens up new potential therapeutic approaches for targeted treatment of GC.
Insights
Circular RNA DYRK1A (circDYRK1A) is downregulated in gastric cancer (GC) and suppresses tumor progression. It inhibits GC cell proliferation, migration, and invasion via the miR-331-5p/GADD45A pathway, offering potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are implicated in cancer progression.
- Aberrant circRNA expression is observed in various malignancies, including gastric cancer (GC).
Purpose of the Study:
- To investigate the role and mechanism of circDYRK1A in gastric cancer progression.
- To explore circDYRK1A as a potential therapeutic target for GC.
Main Methods:
- Bioinformatics and qRT-PCR for expression analysis.
- Sanger sequencing, electrophoresis, and RNase R treatment for structural confirmation.
- Cellular assays (CCK-8, EDU, Transwell) to assess functional impact.
- Dual luciferase, RIP, Western blotting, and rescue assays to validate molecular interactions.
Main Results:
- circDYRK1A was significantly downregulated in GC tissues and cell lines.
- circDYRK1A inhibited GC cell proliferation, migration, and invasion.
- circDYRK1A acts as a sponge for miR-331-5p, upregulating GADD45A.
Conclusions:
- circDYRK1A functions as a tumor suppressor in gastric cancer.
- The circDYRK1A/miR-331-5p/GADD45A axis represents a novel molecular mechanism in GC progression.
- circDYRK1A holds potential as a therapeutic target for gastric cancer treatment.
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