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Published on: September 15, 2023
CircPTK2 Suppresses the Progression of Gastric Cancer by Targeting the MiR-196a-3p/AATK Axis
Ling Gao1, Tingting Xia2, Mingde Qin3
1Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
Background:
Gastric cancer is a type of malignant tumor with high morbidity and mortality. It has been shown that circular RNAs (circRNAs) exert critical roles in gastric cancer progression via working as microRNA (miRNA) sponges to regulate gene expression. However, the role and potential molecular mechanism of circRNAs in gastric cancer remain largely unknown.
Methods:
CircPTK2 (hsa_circ_0005273) was identified by bioinformatics analysis and validated by RT-qPCR assay. Bioinformatics prediction, dual-luciferase reporter, and RNA pull-down assays were used to determine the interaction between circPTK2, miR-196a-3p, and apoptosis-associated tyrosine kinase 1 (AATK).
Results:
The level of circPTK2 was markedly downregulated in gastric cancer tissues and gastric cancer cells. Upregulation of circPTK2 significantly suppressed the proliferation, migration, and invasion of gastric cancer cells, while circPTK2 knockdown exhibited opposite effects. Mechanically, circPTK2 could competitively bind to miR-196a-3p and prevent miR-196a-3p to reduce the expression of AATK. In addition, overexpression of circPTK2 inhibited tumorigenesis in a xenograft mouse model of gastric cancer.
Conclusion:
Collectively, circPTK2 functions as a tumor suppressor to suppress gastric cancer cell proliferation, migration, and invasion through regulating the miR-196a-3p/AATK axis, suggesting that circPTK2 may serve as a novel therapeutic target for gastric cancer.
Insights
Circular RNA PTK2 (circPTK2) acts as a tumor suppressor in gastric cancer. It inhibits cancer cell proliferation, migration, and invasion by regulating the miR-196a-3p/AATK pathway, offering a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gastric cancer is a leading cause of cancer mortality worldwide.
- Circular RNAs (circRNAs) are implicated in cancer progression by sponging microRNAs (miRNAs).
- The specific roles of most circRNAs in gastric cancer remain unclear.
Purpose of the Study:
- To investigate the function and mechanism of circPTK2 in gastric cancer.
- To explore the potential of circPTK2 as a therapeutic target for gastric cancer.
Main Methods:
- Bioinformatics analysis and RT-qPCR to identify and validate circPTK2.
- Dual-luciferase reporter and RNA pull-down assays to confirm molecular interactions.
- In vitro cell assays and in vivo xenograft mouse models to assess tumor suppression.
Main Results:
- circPTK2 expression was significantly downregulated in gastric cancer tissues and cells.
- Overexpression of circPTK2 suppressed gastric cancer cell proliferation, migration, and invasion.
- circPTK2 acts as a sponge for miR-196a-3p, inhibiting its ability to repress AATK expression.
- circPTK2 overexpression inhibited tumor growth in a mouse model.
Conclusions:
- circPTK2 functions as a tumor suppressor in gastric cancer.
- The circPTK2/miR-196a-3p/AATK axis is a key regulatory pathway in gastric cancer.
- circPTK2 represents a promising novel therapeutic target for gastric cancer treatment.
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