叶酸缺乏调控miR-5002-5p-Gadd45α轴抑制结肠癌HCT-116细胞迁移  

Folate deficiency inhibits colorectal cancer HCT-116 cell migration through the miR-5002-5p-Gadd45αaxis

作　　者：曹宇 鲁琳[3] 朱钰倩 郭锡汉[1] 王晗[1] 汪旭[1,5] 倪娟 CAO Yu;LU Lin;ZHU Yuqian;GUO Xihan;WANG Han;WANG Xu;NI Juan(College of Life Sciences,Yunnan Normal University,Yunnan Kunming 650500,China;Yunnan Cancer Institute,Yunnan Cancer Hospital,Yunnan Kunming 650118,China;Institute of Biomedical Engineering,Kunming Medical University,Yunnan Kunming 650500,China;Wuhan Kindstar Dlagnostlcs Co.,Ltd.,Hubei Wuhan 430075,China;Yeda Institute of Gene and Cell Therapy,Zhejiang Taizhou 318000,China)

机构地区：[1]云南师范大学生命科学学院,云南昆明650500 [2]云南省肿瘤医院云南省肿瘤研究所,云南昆明650118 [3]昆明医科大学生物医学工程研究所,云南昆明650500 [4]武汉康圣达医学检验所有限公司,湖北武汉430075 [5]耶大基因与细胞治疗研究所,浙江台州318000

出　　处：《现代肿瘤医学》2025年第4期548-556,共9页Journal of Modern Oncology

基　　金：国家自然科学基金项目(编号:31560307,31860301)。

摘　　要：目的:探讨FA缺乏是否通过miR-5002-5p-Gadd45α轴影响结肠癌细胞的迁移能力。方法:采用双荧光素酶报告实验探究miR-5002-5p与Gadd45α之间的靶向性,RT-qPCR和Western blot检测miR-5002-5p、Gadd45α和E-cadherin在结肠癌细胞系(HCT-116)中的表达水平,Transwell和划痕实验评估细胞迁移能力。结果:在HCT-116细胞中,miR-5002-5p靶向抑制Gadd45α表达;FA缺乏上调Gadd45α表达,抑制细胞迁移和miR-5002-5p表达。沉默Gadd45α或过表达miR-5002-5p抑制Gadd45α表达,都逆转FA缺乏对细胞迁移的抑制作用。FA缺乏可诱导E-cadherin的高表达,且该效应在过表达miR-5002-5p后显著抑制。结论:FA缺乏调控miR-5002-5p-Gadd45α轴抑制HCT-116细胞迁移,该抑制与细胞的上皮间充质状态改变密切相关,Gadd45α是HCT-116细胞响应FA缺乏改变细胞迁移能力的分子靶点。Objective:To investigate whether FA deficiency alters the migration ability of colorectal cancer cells via the miR-5002-5p-Gadd45αaxis.Methods:Dual luciferase reporter assay verified the targeting of miR-5002-5p and Gadd45α3'UTR.The expression of miR-5002-5p,Gadd45αand E-cadherin in colorectal cancer cell line(HCT-116)was detected by RT-qPCR and Western blot.Changes in cell migration were assessed using Transwell and scratch assays.Results:In HCT-116 cells,miR-5002-5p targeted and inhibited Gadd45αexpression.Gadd45αexpression was up-regulated by FA deficiency,and cell migration and miR-5002-5p expression were inhibited.Silencing Gadd45αor overexpressing miR-5002-5p inhibited the expression of Gadd45αand reversed the inhibitory effect of FA deficiency on cell migration.FA deficiency induced high expression of E-cadherin,and this effect was significantly inhibited after overexpression of miR-5002-5p.Conclusion:FA deficiency inhibits HCT-116 cell migration through the miR-5002-5p-Gadd45αaxis,which is closely related to the change of epithelial mesenchymal status of the cells.Gadd45αis the molecular target in FA deficiency changing HCT-116 cell migration ability.

关 键 词：叶酸缺乏 Gadd45α miR-5002-5p 结肠癌 细胞迁移 

分 类 号：R735.3[医药卫生—肿瘤]