CircRNA DUSP16 Knockdown Suppresses Colorectal Cancer Progression by Regulating the miR-432-5p/E2F6 Axis

• Main Authors: Wang G, Yang H
• Format: Article
• Language: English
• Published: Dove Medical Press 2021-08-01
• Series: Cancer Management and Research
• Subjects: circdusp16; mir-432-5p; e2f6; colorectal cancer; progression
• Online Access: https://www.dovepress.com/circrna-dusp16-knockdown-suppresses-colorectal-cancer-progression-by-r-peer-reviewed-fulltext-article-CMAR

Guangyao Wang, Haojun Yang Department of Gastrointestinal Surgery, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, 213000, People’s Republic of ChinaCorrespondence: Haojun YangThe Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, No. 68, Gehu Road, Changzhou, 213000, People’s Republic of ChinaTel [phone]Email [e-mail]: 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.Keywords: circDUSP16, miR-432-5p, E2F6, colorectal cancer, progression