首页|微小RNA-190b-5p靶向调控Smad4及对TGF-β1诱导的直肠癌细胞迁移侵袭和上皮间质转化的影响

微小RNA-190b-5p靶向调控Smad4及对TGF-β1诱导的直肠癌细胞迁移侵袭和上皮间质转化的影响

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目的 探讨微小RNA-190b-5p(miR-190b-5p)对转化生长因子β1(TGF-β1)诱导的直肠癌细胞迁移侵袭和上皮间质转化(EMT)的影响.方法 给予直肠癌SW1463 细胞miR-190b-5p模拟物(mimic)和/或TGF-β1 处理,采用实时荧光定量PCR测定miR-190b-5p表达水平;Western blot检测钙黏蛋白E、波形蛋白和SMAD家族蛋白 4(Smad4)的蛋白表达水平;Transwell实验检测SW1463 细胞的迁移侵袭能力,双荧光素酶报告基因实验验证miR-190b-5p与Smad4 的靶向关系.结果 与正常人结肠上皮细胞 CCD841 con相比,SW1463 细胞的 miR-190b-5p表达降低.TGF-β1 处理诱导 SW1463 细胞的 miR-190b-5p表达水平进一步降低,促进EMT且增强细胞迁移侵袭能力和Smad4 蛋白表达水平.过表达miR-190b-5p可抑制TGF-β1 诱导的EMT及细胞迁移侵袭过程和Smad4 表达上调.结论 miR-190b-5p可能通过抑制Smad4 表达来阻断TGF-β/Smad信号通路诱导的直肠癌细胞EMT和侵袭迁移过程,miR-190b-5p/Smad4 有成为直肠癌治疗靶点的潜能.
Targeting regulation of Smad4 by microRNA-190b-5p and its effect on TGF-β1-induced migration,invasion and epithelial-mesenchymal transition of rectal cancer cells
Objective To explore the role of microRNA-190b-5p(miR-190b-5p)in the transforming growth factor β1(TGF-β1)-induced migration,invasion and epithelial-mesenchymal transformation(EMT)of rectal cancer cells.Methods Rectal cancer SW1463 cells were treated with miR-190b-5p mimic and/or TGF-β1.Real-time fluorescence quantitative PCR was used to measure the expression level of miR-190b-5p.The expressions of E-cadherin,Vimentin and SMAD family member 4(Smad4)were detected by Western blot.Transwell assay was used to detect the migration and invasion abilities of SW1463 cells.Dual luciferase reporter gene experiment was employed to verify the targeting relationship between miR-190b-5p and Smad4.Results Compared with CCD841 con cells,the expression level of miR-190b-5p in SW1463 cells was lower.After TGF-β1 induction,the expression level of miR-190b-5p in SW1463 cells was further decreased,which promoted the occurrence of EMT,enhanced cell migration and invasion,and increased the expression level of Smad4 protein.Overexpression of miR-190b-5p inhibited TGF-β1-induced EMT,weakened cell migration and invasion,and decreased the expression of Smad4 protein level.Conclusion MiR-190b-5p may block TGF-β/Smad signaling pathway-induced EMT,invasion and migration of rectal cancer cells by inhibiting Smad4 expression.MiR-190b-5p/Smad4 has the potential to become a therapeutic target for rectal cancer.

Rectal cancerMicroRNA-190b-5pTransforming growth factor β1SMAD family protein 4Epithelial-mesenchymal transition

王玉豪、张友元

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201500 上海 复旦大学附属金山医院病理科

直肠癌 微小RNA-190b-5p 转化生长因子β1 SMAD家族蛋白4 上皮间质转化

金山区卫生和计划生育委员会青年项目

JSKJ-KTON-2018-13

2024

临床肿瘤学杂志
解放军第八一医院

临床肿瘤学杂志

CSTPCD
影响因子:1.583
ISSN:1009-0460
年,卷(期):2024.29(4)
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