microRNA-1290通过 NDRG1/NF-κB/IL-6信号通路促进结肠癌细胞迁移和侵袭

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Abstract
Objective: To investigate the mechanism of microRNA-1290 （miR-1290） mediating the activation of NF-κB/interleukin-6 （IL-6） signaling by NMyc downstream-regulated gene 1 （NDRG1）, and further explore its impact on the migration and invasion of colorectal carcinoma cells. Methods: Immunohistochemistry were used to detect the expression of IL6 in the tumors and adjacent tissues in 48 cases of colorectal carcinoma. The expression of IL6 and miR-1290 in 20 samples selected at random from the 48 cases, colorectal carcinoma cells and normal colonic epithelial cells, HCoEpiC were detected by qRT-PCR. Western blotting was performed to detect the expression of p-NF-κB, NF-κB, NDRG1, E-cadherin, and vimentin; ELISA was used to test the levels of IL-6 after treatment with miR-1290 inhibitor or mimic, respectively. With the treatment of small interference RNA-IL-6 （siRNA-IL-6） or neutralizing antibody, the effect of miR-1290 in colorectal carcinoma cell migration was assessed by wound healing test, and cell invasion was tested by Matrigel invasion assay. Results: The expression levels of IL-6 were significantly higher in colon cancer tissues than adjacent normal tissues by immunohistochemical staining （P<0.01）, and there was a remarkably positive correlation between miR-1290 and IL-6 mRNA in colorectal carcinoma tissues （r=0.845 4, P<0.01）. Moreover, the expression of miR-1290 in colon cancer cells were significantly higher than in HCoEpiC cell （all P<0.01）. Upregulation of miR1290 by mimic inhibited the expression of NDRG1 and further induced the activation of NF-κB pathway and epithelial mesenchymal transformation（P<0.01）, while the treatment of miR-1290 inhibitor restored the expression of NDRG1 but increased the expression of p-NF-κB（P<0.01）. The scratch results showed miR-1290 upregulation increased the healing rate of colorectal carcinoma cells, which could be blocked by IL-6 silencing（P<0.01）. Coincidently, the number of invasive cells were elevated after miR-1290 mimic treatment, which could be effectively reversed by neutralizing antibody of IL-6（P<0.01）. Conclusion: miR-1290 promotes migration and invasion of colorectal carcinoma cell through the NF-κB/IL-6 axis, which is caused by targeting inhibition of NDRG1.

Received: 09 June 2020

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	MO Hui
	XU Min

Cite this article:

MO Hui,XU Min.

microRNA-1290 promotes migration and invasion of colorectal carcinoma cell via NDRG1/NF-κB/IL-6 pathway

[J]. Journal of Jiangsu University(Medicine Edition), 2021, 31(04): 277-283.

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http://zzs.ujs.edu.cn/xbyxb/EN/ OR http://zzs.ujs.edu.cn/xbyxb/EN/Y2021/V31/I04/277

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