首页|微小RNA-483-5p调控TIMP2表达对膀胱癌细胞增殖和侵袭的影响

微小RNA-483-5p调控TIMP2表达对膀胱癌细胞增殖和侵袭的影响

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目的 探讨微小RNA-483-5p(miR-483-5p)对膀胱癌(BC)细胞增殖、迁移和侵袭的影响,并初步分析其可能的分子机制.方法 通过TCGA数据库分析miR-483-5p在BC组织中的表达及与预后的关系,荧光实时定量PCR检测BC细胞T24 中miR-483-5p和金属蛋白酶组织抑制因子(TIMP)-2的表达水平.将miR-483-5p模拟物(mimic)和阻碍物(inhibitor)转染T24 细胞,应用CCK-8和Transwell法评估miR-483-5p对T24 细胞增殖和迁移侵袭的影响.双荧光素酶报告基因实验分析miR-483-5p和TIMP-2间的靶向关系,挽救实验验证miR-483-5p的生物学功能是否通过TIMP-2 发挥作用.结果 与癌旁组织比较,BC组织中高表达miR-483-5p(P<0.05),高表达miR-483-5p者的总生存率低于低表达者(P<0.05).miR-483-5p mimic可促进T24 细胞的增殖、迁移和侵袭能力(P<0.05),miR-483-5p inhibitor则抑制T24 细胞的增殖、迁移和侵袭能力(P<0.05).TIMP2 为miR-483-5p的下游靶点,干扰TIMP2 可逆转miR-483-5p下调对T24 细胞增殖、迁移和侵袭的抑制作用(P<0.05).结论 miR-483-5p在BC中高表达,与BC患者不良预后相关.miR-483-5p可下调TIMP2 的表达来促进BC细胞的增殖、迁移和侵袭.
Targeted-regulation of TIMP2 expression by microRNA-483-5p and its effect on the proliferation and invasion of bladder cancer cells
Objective To investigate the impact of microRNA-483-5p(miR-483-5p)on the proliferation,migration,and invasion of bladder cancer(BC)cells as well as its potential molecular mechanism.Methods The expression of miR-483-5p in BC tissues and its relationship with prognosis were analyzed by TCGA database.Fluorescence-based real-time quantitative PCR was used to analyze the expression levels of miR-483-5p and tissue inhibitor of matrix metalloproteinases(TIMP)-2 in BC T24 cells.Transfection of miR-483-5p mimic and inhibitor was performed in T24 cells.The impact of miR-483-5p on cellular proliferation was evaluated through the implementation of a CCK-8 assay.Migration and invasion capabilities of T24 cells were assessed utilizing Transwell assays.The targeted interaction between miR-483-5p and TIMP-2 was demonstrated using a dual-luciferase reporter gene assay.Rescue experiments was performed to verify whether the biological functions of miR-483-5p play a role through TIMP-2.Results The expression of miR-483-5p in BC tissues was significantly higher compared to adjacent tissues(P<0.05).Patients with high expression of miR-483-5p exhibited a lower overall survival rate than those with low expression(P<0.05).The miR-483-5p mimic significantly enhanced the proliferation,migration,and invasion capacities of T24 cells(P<0.05).The inhibition of miR-483-5p resulted in a significant decrease in proliferation,migration and invasion capacities of T24 cells(P<0.05).The downstream targeted gene of miR-483-5p,TIMP2,was found to be involved in regulating proliferation,migration and invasion capacities of T24 cells(P<0.05).Furthermore,the downregulation effects of miR-483-5p on these cellular processes can be reversed by using interfering TIMP2.Conclusion The expression of miR-483-5p is upregulated in BC and correlates with unfavorable prognosis in BC patients.Moreover,miR-483-5p exerts its oncogenic effects by suppressing the expression of TIMP2,thereby promoting proliferation,migration,and invasion of BC cells.

Bladder cancerMicroRNA-483-5pTissue inhibitor of matrix metalloproteinases-2ProliferationInvasion

张甜甜、邹震海、郭园园、汪蕊

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233003 安徽蚌埠 蚌埠医学院第一附属医院肿瘤内科

224000 江苏省盐城市第三人民医院泌尿外科

233003 安徽省蚌埠市蚌埠医学院第一附属医院泌尿外科

膀胱癌 微小RNA-483-5p 金属蛋白酶组织抑制因子2 增殖 侵袭

蚌埠医学院自然科学重点项目蚌埠医学院"512"中青年骨干教师人才项目

2020byzd064by51201215

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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