Colorectal cancer (CRC) is one of the most common malignant tumours. The recurrence and metastasis of CRC seriously affect the survival rate of patients. Angiogenesis is an extremely important cause of tumour growth and metastasis. Circular RNAs (circRNAs) have been emerged as vital regulators for tumour progression. However, the regulatory role, clinical significance and underlying mechanisms still remain largely unknown. High-throughput sequencing was used to analyse differential circRNAs expression in tumour and non-tumour tissues of CRC. In situ hybridization (ISH) and qRT-PCR were used to determine the level of circ3823 in CRC tissues and serum samples. Then, functional experiments in vitro and in vivo were performed to investigate the effects of circ3823 on tumour growth, metastasis and angiogenesis in CRC. Sanger sequencing, RNase R and Actinomycin D assay were used to verify the ring structure of circ3823. Mechanistically, dual luciferase reporter assay, fluorescent in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down experiments were performed to confirm the underlying mechanisms of circ3823. Circ3823 was evidently highly expressed in CRC and high circ3823 expression predicted a worse prognosis of CRC patients. Receiver operating characteristic curves (ROCs) indicated that the expression of circ3823 in serum showed high sensitivity and specificity for detecting CRC which means circ3823 have the potential to be used as diagnostic biomarkers. Functional experiments in vitro and in vivo indicated that circ3823 promote CRC cell proliferation, metastasis and angiogenesis. Mechanism analysis showed that circ3823 act as a competing endogenous RNA of miR-30c-5p to relieve the repressive effect of miR-30c-5p on its target TCF7 which upregulates MYC and CCND1, and finally facilitates CRC progression. In addition, we found that N6-methyladenosine (m6A) modification exists on circ3823. And the m6A modification is involved in regulating the degradation of circ3823. Our findings suggest that circ3823 promotes CRC growth, metastasis and angiogenesis through circ3823/miR-30c-5p/TCF7 axis and it may serve as a new diagnostic marker or target for treatment of CRC patients. In addition, m6A modification is involved in regulating the degradation of circ3823.

中文翻译：

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Circ3823 有助于结直肠癌的生长、转移和血管生成：miR-30c-5p/TCF7 轴的参与

结直肠癌（CRC）是最常见的恶性肿瘤之一。结直肠癌的复发和转移严重影响患者的生存率。血管生成是肿瘤生长和转移的极其重要的原因。环状 RNA (circRNA) 已成为肿瘤进展的重要调节因子。然而，调节作用、临床意义和潜在机制仍然很大程度上未知。高通量测序用于分析 CRC 肿瘤和非肿瘤组织中差异 circRNAs 的表达。原位杂交 (ISH) 和 qRT-PCR 用于确定 CRC 组织和血清样本中 circ3823 的水平。然后，进行了体外和体内功能实验，以研究 circ3823 对 CRC 肿瘤生长、转移和血管生成的影响。桑格测序，核糖核酸酶 R 和放线菌素 D 测定用于验证 circ3823 的环结构。在机制上，进行了双荧光素酶报告基因测定、荧光原位杂交 (FISH)、RNA 免疫沉淀 (RIP) 和 RNA 下拉实验，以确认 circ3823 的潜在机制。Circ3823 在 CRC 中明显高表达，circ3823 高表达预示着 CRC 患者的预后较差。受试者工作特征曲线 (ROCs) 表明，circ3823 在血清中的表达对检测 CRC 具有较高的敏感性和特异性，这意味着 circ3823 具有用作诊断生物标志物的潜力。体外和体内功能实验表明，circ3823 促进 CRC 细胞增殖、转移和血管生成。机制分析表明，circ3823 作为 miR-30c-5p 的竞争性内源性 RNA，可减轻 miR-30c-5p 对其靶标 TCF7 的抑制作用，从而上调 MYC 和 CCND1，最终促进 CRC 进展。此外，我们发现circ3823上存在N6-甲基腺苷（m6A）修饰。m6A修饰参与调节circ3823的降解。我们的研究结果表明，circ3823 通过 circ3823/miR-30c-5p/TCF7 轴促进 CRC 生长、转移和血管生成，它可能作为一种新的诊断标志物或治疗 CRC 患者的靶点。此外，m6A 修饰参与调控 circ3823 的降解。我们发现 circ3823 上存在 N6-甲基腺苷 (m6A) 修饰。m6A修饰参与调节circ3823的降解。我们的研究结果表明，circ3823 通过 circ3823/miR-30c-5p/TCF7 轴促进 CRC 生长、转移和血管生成，它可能作为一种新的诊断标志物或治疗 CRC 患者的靶点。此外，m6A 修饰参与调控 circ3823 的降解。我们发现 circ3823 上存在 N6-甲基腺苷 (m6A) 修饰。m6A修饰参与调节circ3823的降解。我们的研究结果表明，circ3823 通过 circ3823/miR-30c-5p/TCF7 轴促进 CRC 生长、转移和血管生成，它可能作为一种新的诊断标志物或治疗 CRC 患者的靶点。此外，m6A 修饰参与调控 circ3823 的降解。