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CircRNA DUSP16 Knockdown Suppresses Colorectal Cancer Progression by Regulating the miR-432-5p/E2F6 Axis
1Department of Gastrointestinal Surgery, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, 213000, People's Republic of China.
Background:
Circular RNAs (circRNAs) play critical roles in various types of cancer. The aim of the present study was to investigate the function and underlying mechanism of CircRNA DUSP16 (circDUSP16) in colorectal cancer (CRC) development.
Materials And Methods:
The expression levels of circDUSP16, microRNA-432-5p (miR-432-5p), and E2F transcription factor 6 (E2F6) were measured by RT-qPCR. Cell proliferation, migration, invasion, and apoptosis were investigated by CCK-8, Transwell, and flow cytometry assays. Western blot analysis was used to evaluate the levels of the pro-apoptotic protein (Bax and cleaved-caspase 3) and the anti-apoptotic protein (Bcl-2). Luciferase reporter assay and RIP assay were used to analyze the association between miR-432-5p and circDUSP16 or E2F6. A xenograft tumor model was employed to explore the effect of circDUSP16 on CRC tumor growth in vivo.
Results:
CircDUSP16 expression was upregulated in CRC tissues and cell lines. High circDUSP16 expression was correlated with low survival rate. Furthermore, circDUSP16 knockdown repressed cell proliferation, migration, and invasion and induced apoptosis in CRC. CircDUSP16 caused a negative regulation in miR-432-5p expression. In addition, E2F6 expression was elevated in CRC tissues. Inhibition of miR-432-5p promoted the proliferative and metastatic activity of CRC cells and inhibited the induction of apoptosis. Inhibition of E2F6 expression partially abolished the effects caused by miR-432-5p depletion. Moreover, circDUSP16 upregulated E2F6 expression by reducing miR-432-5p expression. Furthermore, circDUSP16 silencing repressed CRC tumor growth in vivo.
Conclusion:
The results supported the hypothesis that circDUSP16 knockdown suppressed CRC progression by regulating the miR-432-5p/E2F6 axis, suggesting that the circDUSP16/miR-432-5p/E2F6 network may be a potential therapeutic target for CRC.
Insights
Circular RNA DUSP16 (circDUSP16) promotes colorectal cancer (CRC) by upregulating E2F6 via sponging miR-432-5p. Silencing circDUSP16 inhibits CRC progression and tumor growth, offering a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are implicated in various cancers.
- The role of circRNA DUSP16 (circDUSP16) in colorectal cancer (CRC) remains largely unexplored.
Purpose of the Study:
- To investigate the function of circDUSP16 in colorectal cancer development.
- To elucidate the underlying molecular mechanism of circDUSP16 in CRC.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) for gene expression analysis.
- Cellular assays (CCK-8, Transwell, flow cytometry) for proliferation, migration, invasion, and apoptosis.
- Western blot for apoptosis-related proteins.
- Luciferase reporter and RNA immunoprecipitation (RIP) assays for molecular interactions.
- In vivo xenograft tumor model to assess tumor growth.
Main Results:
- CircDUSP16 was upregulated in CRC tissues and cell lines, correlating with poor survival.
- Knockdown of circDUSP16 suppressed CRC cell proliferation, migration, invasion, and induced apoptosis.
- CircDUSP16 positively regulated E2F6 expression by negatively regulating miR-432-5p.
- CircDUSP16 silencing repressed CRC tumor growth in vivo.
Conclusions:
- CircDUSP16 knockdown suppresses CRC progression by modulating the miR-432-5p/E2F6 axis.
- The circDUSP16/miR-432-5p/E2F6 network represents a potential therapeutic target for colorectal cancer.
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