Abstract:
Objective: To investigate the mechanism of microRNA-1290 (miR-1290) mediating the activation of NF-κB/interleukin-6 (IL-6) signaling by NMyc 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 IL6 in the tumors and adjacent tissues in 48 cases of colorectal carcinoma. The expression of IL6 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 miR1290 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.
收稿日期: 2020-06-09
基金资助:国家自然科学基金资助项目(81672402)
通讯作者:
徐岷(通讯作者),教授,主任医师,E-mail:peterxu1974@163.com
作者简介: 莫辉(1993—),男,硕士研究生
引用本文:
莫辉, 徐岷. 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[J]. 江苏大学学报:医学版, 2021, 31(04): 277-283.
MO Hui, XU Min.
microRNA-1290 promotes migration and invasion of colorectal carcinoma cell via NDRG1/NF-κB/IL-6 pathway
. Journal of Jiangsu University(Medicine Edition), 2021, 31(04): 277-283.
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