Circ3823 contributes to growth, metastasis and angiogenesis of colorectal cancer: involvement of miR-30c-5p/TCF7 axis.
Circ3823 contributes to growth, metastasis and angiogenesis of colorectal cancer: involvement of miR-30c-5p/TCF7 axis.
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DOI：
10.1186/s12943-021-01372-0
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发表时间：
2021-06-25
期刊：
影响因子：
37.3
通讯作者：
Ji Z
中科院分区：
文献类型：
--
作者：
Guo Y;Guo Y;Chen C;Fan D;Wu X;Zhao L;Shao B;Sun Z;Ji Z
结直肠癌（CRC）是最常见的恶性肿瘤之一。结直肠癌的复发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一个极其重要的原因。环状rna （circRNAs）已成为肿瘤进展的重要调节因子。然而，其调控作用、临床意义和潜在机制仍不甚清楚。采用高通量测序分析CRC肿瘤组织和非肿瘤组织中环状rna的差异表达。采用原位杂交（ISH）和qRT-PCR检测CRC组织和血清样本中circ3823的表达水平。通过体外和体内功能实验研究circ3823对结直肠癌肿瘤生长、转移和血管生成的影响。采用Sanger测序、RNase R和放线菌素D检测验证circ3823的环结构。机制上，通过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拉下实验来证实circ3823的潜在机制。Circ3823在结直肠癌中明显高表达，高表达预示结直肠癌患者预后较差。受试者工作特征曲线（roc）显示circ3823在血清中的表达对CRC的检测具有较高的敏感性和特异性，这意味着circ3823具有作为诊断性生物标志物的潜力。体外和体内功能实验表明，circ3823促进结直肠癌细胞增殖、转移和血管生成。机制分析表明，circ3823作为miR-30c-5p的竞争内源性RNA，缓解miR-30c-5p对其靶点TCF7的抑制作用，从而上调MYC和CCND1，最终促进CRC的进展。此外，我们发现在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轴促进结直肠癌的生长、转移和血管生成，可能成为结直肠癌患者新的诊断标志物或治疗靶点。此外，m6A修饰参与调节circ3823的降解。在线版本包含补充材料，可在10.1186/s12943-021-01372-0获得。
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. The online version contains supplementary material available at 10.1186/s12943-021-01372-0.
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影响因子：
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