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首页> 外文期刊>Biological chemistry >Circular RNA hsa_circ_0001178 facilitates the invasion and metastasis of colorectal cancer through upregulating ZEB1 via sponging multiple miRNAs
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Circular RNA hsa_circ_0001178 facilitates the invasion and metastasis of colorectal cancer through upregulating ZEB1 via sponging multiple miRNAs

机译：圆形RNA HSA_CIRC_0001178促进通过海绵型多个miRNA通过上调Zeb1的结肠直肠癌的侵袭和转移

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摘要

Metastasis is the main cause of increasing cancer morbidity and mortality. However, the underlying mechanism of cancer metastasis remains largely unknown. In the present study, we identified one circular RNA (circRNA) closely related to the metastasis of colorectal cancer (CRC), namely hsa_circ_0001178. CRC patients with high hsa_circ_0001178 were more prone to have metastatic clinical features, advanced TNM stage and adverse prognosis. Stable knockdown of hsa_circ_0001178 significantly weakened CRC cell migratory and invasive capabilities in vitro as well as lung and liver metastases in vivo. Mechanistic study revealed that hsa_circ_0001178 acted as a competing endogenous RNA (ceRNA) for miR-382/587/616 to upregulate ZEB1 (a key trigger of epithelial-to-mesenchymal transition), thereby promoting CRC metastatic dissemination. Of note, ZEB1 could also increase hsa_circ_0001178 expression via physically binding to hsa_circ_0001178 promoter region. Collectively, our data uncover the crucial role of hsa_circ_0001178 in CRC metastasis, and targeted therapy based on this positive feedback ceRNA axis may be a promising treatment for metastatic CRC patients.
机译：转移是增加癌症发病率和死亡率的主要原因。然而，癌症转移的潜在机制仍然很大程度上是未知的。在本研究中，我们鉴定了与结直肠癌（CRC）转移密切相关的一种圆形RNA（CircrNA），即HSA_CIRC_0001178。 CRC患者高HSA_CIRC_0001178易患转移性临床特征，晚期TNM阶段和不良预后。 HSA_CIRC_0001178的稳定敲低在体外较弱的CRC细胞迁移和侵入性能力和体内肺和肝转移。机械研究表明，HSA_CIRC_0001178用作MIR-382/587/616的竞争内源性RNA（CERNA），以上调ZEB1（上皮 - 间充质转变的关键触发），从而促进CRC转移性筛选。值得注意的是，通过物理结合HSA_CIRC_0001178启动子区域，ZEB1也可以增加HSA_CIRC_0001178表达。集体，我们的数据揭示了HSA_CIRC_0001178在CRC转移中的关键作用，基于该阳性反馈Cerna轴的靶向治疗可能是转移CRC患者的有希望的治疗方法。

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