Background: CircRNA circ_0026344 was previously revealed as a tumour-suppressive gene in colorectal cancer (CRC) progression. The purpose of this research was to investigate the role of circ_0026344 in CRC cells metastasis induced by chemokines. Methods: Two human CRC cell lines SW480 and Caco-2 were treated by CCL20 and CXCL8. Cell proliferation, migration/invasion, expression of epithelial-mesenchymal transition (EMT) inducers and the expression of circ_0026344 were measured using sulforhodamine B assay, Transwell chamber, western blot and qRT-PCR, respectively. The effects of circ_0026344 on CRC cells migration/invasion and the expression of EMT inducers were evaluated. Moreover, the downstream miRNA and signalling pathways of circ_0026344 were studied. Results: CCL20 and CXCL8 synergized to facilitate the proliferation, migration and invasion of CRC cells. At the meantime, E-cadherin was downregulated, whereas N-cadherin, Vimentin and Snail were up-regulated by CCL20 and CXCL8 co-stimulation, which was accompanied by the mobilization of PI3K/AKT/ERK signalling. More interestingly, the expression of circ_0026344 was down-regulated by CCL20 and CXCL8 co-stimulation. Silence of circ_0026344 increased the migratory and invasive capacities of CRC cells and increased EMT process as well. Overexpression of circ_0026344 led to a contrary impact. miR-183 was negatively regulated by circ_0026344, and the inhibitory effects of circ_0026344 overexpression on Wnt/β-catenin pathway were reversed when miR-183 was overexpressed. Conclusion: Overexpression of circ_0026344 restrained CRC metastasis and EMT induced by CCL20 and CXCL8 synergistical treatment. miR-183 was a downstream effector of circ_0026344, and the anti-tumour function of circ_0026344 might be involved in the repressed Wnt/β-catenin signalling. Highlights CCL20 and CXCL8 synergize to decrease the expression of circ_0026344; Silence of circ_0026344 promotes CRC cells migration, invasion and EMT process; miR-183 is a downstream effector of circ_0026344.

中文翻译：

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Circ_0026344 通过 miR-183 抑制人结直肠癌细胞的转移。

背景：CircRNA circ_0026344 先前被揭示为结直肠癌 (CRC) 进展中的肿瘤抑制基因。本研究旨在探讨circ_0026344在趋化因子诱导的CRC细胞转移中的作用。方法：用CCL20和CXCL8处理两种人CRC细胞系SW480和Caco-2。细胞增殖、迁移/侵袭、上皮间质转化 (EMT) 诱导剂的表达和 circ_0026344 的表达分别使用 sulforhodamine B 测定、Transwell 室、蛋白质印迹和 qRT-PCR 进行测量。评估了 circ_0026344 对 CRC 细胞迁移/侵袭和 EMT 诱导剂表达的影响。此外，还研究了circ_0026344的下游miRNA和信号通路。结果：CCL20和CXCL8协同促进增殖，CRC细胞的迁移和侵袭。同时，E-cadherin 下调，而 N-cadherin、Vimentin 和 Snail 在 CCL20 和 CXCL8 共刺激下上调，伴随着 PI3K/AKT/ERK 信号的动员。更有趣的是，circ_0026344 的表达被 CCL20 和 CXCL8 共同刺激下调。circ_0026344 的沉默增加了 CRC 细胞的迁移和侵袭能力，也增加了 EMT 过程。circ_0026344 的过度表达导致了相反的影响。miR-183 受 circ_0026344 负调控，当 miR-183 过表达时，circ_0026344 过表达对 Wnt/β-catenin 通路的抑制作用被逆转。结论：circ_0026344的过表达抑制了CCL20和CXCL8协同治疗诱导的CRC转移和EMT。miR-183 是 circ_0026344 的下游效应子，circ_0026344 的抗肿瘤功能可能参与抑制的 Wnt/β-catenin 信号传导。亮点 CCL20 和 CXCL8 协同降低 circ_0026344 的表达；circ_0026344的沉默促进CRC细胞迁移、侵袭和EMT过程；miR-183 是 circ_0026344 的下游效应子。