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Circ_0049447 acts as a tumor suppressor in gastric cancer through reducing proliferation, migration, invasion, and
Kai-Wen Tang1, Zhe-Xu Guo, Zhong-Hua Wu
1Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China.
Background:
Although increasing abnormal expression of circular RNAs (circRNAs) has been revealed in various cancers, there were a small number of studies about circRNAs in gastric cancer (GC). Here, we explored the expression and function of a novel circRNA, circ_0049447, in GC.
Methods:
A total of 80 GC tissues and non-tumorous tissues were collected from the First Affiliated Hospital of China Medical University. And all cells were cultured with 10% fetal bovine serum and incubated at 37°C and 5% CO2. The expression of circ_0049447 was quantified by real-time polymerase chain reaction. The biological function of circ_0049447 on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) was evaluated by cell counting kit-8 (CCK-8), colony formation assay, transwell migration and invasion assay, and Western blotting. Luciferase report assay was used to verify the direct binding between circ_0049447 and predicted microRNA (miRNA). Furthermore, a xenograft mouse model was used to validate the function of circ_0049447 in vivo.
Results:
We demonstrated that circ_0049447 was downregulated in GC (P < 0.001). The area under the receiver operating characteristic curve reached 0.838, while sensitivity was 82.3% and specificity was 77.2%. CCK-8 and colony formation assay showed that overexpression of circ_0049447 could inhibit the proliferation (P < 0.05). Transwell migration and invasion assay showed upregulated circ_0049447 could impede migration in GC cells (P < 0.05). In addition, overexpression of circ_0049447 could impede GC cell EMT. Upregulation of miR-324-5p in GC specimens and direct binding between miR-324-5p with circ_0049447 proven by luciferase reporter assay indicated that circ_0049447 may inhibit GC by sponging certain miRNA.
Conclusion:
Circ_0049447 acts as a tumor suppressor in GC through reducing proliferation, migration, invasion, and EMT, and it is a promising biomarker for diagnosis.
Insights
Circular RNA circ_0049447 is downregulated in gastric cancer (GC) and acts as a tumor suppressor. This novel circRNA inhibits GC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), showing diagnostic potential.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) show altered expression in various cancers.
- Limited research exists on circRNAs in gastric cancer (GC).
- This study investigates the novel circRNA, circ_0049447, in GC.
Purpose of the Study:
- To explore the expression and function of circ_0049447 in gastric cancer.
- To determine if circ_0049447 acts as a tumor suppressor in GC.
- To evaluate circ_0049447 as a potential diagnostic biomarker for GC.
Main Methods:
- Quantified circ_0049447 expression in 80 GC tissues and adjacent non-tumorous tissues using real-time PCR.
- Assessed the functional impact of circ_0049447 on GC cell proliferation, migration, invasion, and EMT in vitro.
- Utilized luciferase reporter assays and a xenograft mouse model to validate molecular mechanisms and in vivo function.
Main Results:
- Circ_0049447 was significantly downregulated in GC tissues (P < 0.001) with diagnostic potential (AUC=0.838).
- Overexpression of circ_0049447 inhibited GC cell proliferation, migration, invasion, and EMT.
- Confirmed direct binding between circ_0049447 and miR-324-5p, suggesting a miRNA sponging mechanism.
Conclusions:
- Circ_0049447 functions as a tumor suppressor in gastric cancer.
- It inhibits key cancer hallmarks including proliferation, migration, invasion, and EMT.
- Circ_0049447 represents a promising biomarker for GC diagnosis and potential therapeutic target.
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