Circular RNA hsa_circ_0001178 facilitates the invasion and metastasis of colorectal cancer through upregulating ZEB1 via sponging multiple miRNAs
Circular RNA hsa_circ_0001178 facilitates the invasion and metastasis of colorectal cancer through upregulating ZEB1 via sponging multiple miRNAs
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DOI：
10.1515/hsz-2019-0350
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发表时间：
2020-04-01
影响因子：
3.7
通讯作者：
Wang, Wanhai
中科院分区：
文献类型：
--
作者：
Ren, Chunfeng;Zhang, Zhenmin;Wang, Wanhai
转移是癌症发病率和死亡率上升的主要原因。然而，癌症转移的潜在机制在很大程度上仍然未知。在本研究中，我们发现了一个与结直肠癌（CRC）转移密切相关的环状RNA (circRNA)，即hsa_circ_0001178。高hsa_ circ_0001178的CRC患者更容易出现转移性临床特征、恶性肿瘤晚期和不良预后。稳定敲低hsa_circ_0001178显著削弱CRC细胞在体外的迁移和侵袭能力，以及体内的肺和肝转移。机制研究显示，hsa_circ_0001178作为miR-382/587/616的竞争内源性RNA （ceRNA）上调ZEB1（上皮-间质转化的关键触发因子），从而促进CRC转移传播。值得注意的是，ZEB1也可以通过物理结合hsa_circ_0001178启动子区来增加hsa_circ_0001178的表达。总之，我们的数据揭示了hsa_circ_0001178在CRC转移中的关键作用，基于这种正反馈ceRNA轴的靶向治疗可能是转移性CRC患者的一种有希望的治疗方法。
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 NM 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.