Circ_0026344 restrains metastasis of human colorectal cancer cells via miR-183 (Publication with Expression of Concern. See vol. 49, pg. 673, 2021)
Circ_0026344 restrains metastasis of human colorectal cancer cells via miR-183 (Publication with Expression of Concern. See vol. 49, pg. 673, 2021)
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DOI：
10.1080/21691401.2019.1669620
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发表时间：
2019-12-04
影响因子：
5.8
通讯作者：
Li, Yunfeng
中科院分区：
文献类型：
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作者：
Shen, Tao;Cheng, Xianshuo;Li, Yunfeng
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。本研究的目的是探讨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。分别使用磺胺罗丹明 B 测定、Transwell 小室、蛋白质印迹和 qRT-PCR 测量细胞增殖、迁移/侵袭、上皮间质转化 (EMT) 诱导剂的表达和 circ_0026344 的表达。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CRC细胞的增殖、迁移和侵袭。同时，CCL20 和 CXCL8 共刺激使 E-cadherin 下调，而 N-cadherin、Vimentin 和 Snail 上调，并伴随着 PI3K/AKT/ERK 信号传导的动员。更有趣的是，CCL20和CXCL8共刺激下调了circ_0026344的表达。 circ_0026344的沉默增加了CRC细胞的迁移和侵袭能力，并增加了EMT过程。 circ_0026344 的过度表达导致了相反的影响。 miR-183受到circ_0026344的负向调节，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的抗肿瘤功能可能与抑制的Wnt/β-catenin信号传导有关。
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/?-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/?-catenin signalling.