CircFoxo3 knockdown inhibit gastric cancer progression by regulating Foxo3
Huiling Yu1,2, Qijin He1, Ping Li1
1Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin Medical University General Hospital, No. 154 Anshan Road, Tianjin, 300052, China.
Abstract:
Improving the diagnosis and treatment of gastric cancer is a significant challenge worldwide. Circular RNAs (circRNAs), a recently identified class of endogenous non-coding RNAs with covalently closed-loop structures, have emerged as key regulators in tumorigenesis. CircFoxo3 has been studied in various cancer types, while its functional role in GC remains poorly understood. In this study, we found that circFoxo3 is significantly upregulated in GC tissues and cell lines compared to paired normal controls. Functional analyses demonstrated that knockdown of circFoxo3 markedly inhibited GC cell proliferation and migration, whereas overexpression of circFoxo3 produced the opposite effects. Mechanistically, circFoxo3 knockdown reduced forkhead box (Fox) transcription factors FOXO3 mRNA and protein levels. FOXO3a is involved in regulating cancer cell proliferation. Bioinformatic analysis revealed high expression of FOXO3 in GC tumor samples, a finding confirmed in both GC tissues and cell lines. A tumor xenograft model was used to examine the effect of circFoxo3 on tumor growth in vivo. The low circFoxo3 expression reduced the volume of the tumor and decreased its proliferation. Collectively, our findings identify circFoxo3 as an oncogenic factor in GC progression.
Insights
Circular RNAs (circRNAs) like circFoxo3 are upregulated in gastric cancer (GC). Reducing circFoxo3 inhibits GC cell growth and migration, identifying it as a potential therapeutic target for gastric cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gastric cancer (GC) diagnosis and treatment remain challenging globally.
- Circular RNAs (circRNAs) are emerging as key regulators in tumorigenesis.
- The specific role of circFoxo3 in GC progression is not well understood.
Purpose of the Study:
- To investigate the functional role of circFoxo3 in gastric cancer.
- To determine the mechanism by which circFoxo3 influences GC cell behavior.
- To evaluate circFoxo3 as a potential biomarker or therapeutic target for GC.
Main Methods:
- Quantitative real-time PCR to assess circFoxo3 and FOXO3 expression in GC tissues and cell lines.
- Cell proliferation and migration assays (e.g., EdU, Transwell) following circFoxo3 knockdown or overexpression.
- Western blotting to analyze protein levels of FOXO3.
- Bioinformatic analysis of public databases for FOXO3 expression in GC.
- In vivo tumor xenograft models to assess the effect of circFoxo3 on tumor growth.
Main Results:
- CircFoxo3 expression was significantly upregulated in GC tissues and cell lines compared to normal controls.
- Knockdown of circFoxo3 inhibited GC cell proliferation and migration, while overexpression promoted these processes.
- CircFoxo3 knockdown led to reduced mRNA and protein levels of the transcription factor FOXO3.
- High expression of FOXO3 was observed in GC tumor samples, consistent with findings in tissues and cell lines.
- In vivo studies showed that reduced circFoxo3 expression decreased tumor volume and proliferation.
Conclusions:
- CircFoxo3 acts as an oncogenic factor promoting gastric cancer progression.
- CircFoxo3 influences GC cell proliferation and migration, partly through regulating FOXO3.
- CircFoxo3 represents a potential diagnostic marker and therapeutic target for gastric cancer.
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