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.



中文翻译：

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CircRNA DUSP16 敲低通过调节 miR-432-5p/E2F6 轴抑制结直肠癌进展

背景：环状 RNA (circRNA) 在各种类型的癌症中发挥着关键作用。本研究的目的是探讨 CircRNA DUSP16 (circDUSP16) 在结直肠癌 (CRC) 发展中的功能和潜在机制。
材料和方法：通过 RT-qPCR 测量 circDUSP16、microRNA-432-5p (miR-432-5p) 和 E2F 转录因子 6 (E2F6) 的表达水平。通过 CCK-8、Transwell 和流式细胞术检测细胞增殖、迁移、侵袭和凋亡。Western印迹分析用于评估促凋亡蛋白（Bax和cleaved-caspase 3）和抗凋亡蛋白（Bcl-2）的水平。荧光素酶报告基因分析和RIP分析用于分析miR-432-5p与circDUSP16或E2F6之间的关联。采用异种移植肿瘤模型来探索 circDUSP16 对体内 CRC 肿瘤生长的影响。
结果：CircDUSP16 表达在 CRC 组织和细胞系中上调。circDUSP16 高表达与低存活率相关。此外，circDUSP16 敲低可抑制 CRC 中的细胞增殖、迁移和侵袭，并诱导细胞凋亡。CircDUSP16 引起 miR-432-5p 表达的负调节。此外，CRC 组织中 E2F6 表达升高。抑制 miR-432-5p 可促进 CRC 细胞的增殖和转移活性，并抑制细胞凋亡的诱导。E2F6 表达的抑制部分消除了由 miR-432-5p 消耗引起的影响。此外，circDUSP16 通过降低 miR-432-5p 表达上调 E2F6 表达。此外，circDUSP16 沉默抑制了体内 CRC 肿瘤的生长。
结论：结果支持了 circDUSP16 敲低通过调节 miR-432-5p/E2F6 轴抑制 CRC 进展的假设，表明 circDUSP16/miR-432-5p/E2F6 网络可能是 CRC 的潜在治疗靶点。