miR-4677-3p靶向抑制MMP2对食管鳞癌细胞体外增殖和迁移的影响OA
Effect of miR-4677-3p Targeted Inhibition of MMP2 on the Proliferation and Migration of Esophageal Squamous Cell Carcinoma Cells in Vitro
目的 探讨miR-4677-3p靶向调控基质金属蛋白酶-2(MMP 2)对食管鳞癌(ESCC)细胞体外增殖和迁移的影响及其分子机制.方法 基于GEO数据库GSE263647 数据集,通过生物信息学分析筛选ESCC预后相关的关键基因MMP 2,并采用miRWalk和miRDB数据库预测靶向MMP 2 的miRNA;通过qRT-PCR和Western blot检测人正常食管上皮细胞(HEEC)及 4 种ESCC细胞系中MMP 2 的mRNA和蛋白表达水平;利用siRNA转染和慢病毒感染技术分别在KYSE-150 和KYSE-70 细胞中建立MMP 2 敲降和过表达模型;通过CCK-8 实验评估细胞增殖能力,采用划痕实验检测细胞迁移能力;通过转染miR-4677-3p摸拟物和抑制剂,验证其对MMP 2 表达的调控作用.结果 筛选出 467 个差异表达基因和 89 个潜在调控miRNA,MMP 2 在ESCC组织及细胞系中显著高表达,且与患者不良预后相关.功能学实验表明:与对照组相比,si-MMP 2 敲降组细胞的增殖和迁移能力降低,过表达组则相反;miR-4677-3p摸拟物转染使MMP 2 蛋白表达水平下调,且细胞的增殖和迁移能力降低,miR-4677-3p抑制剂组则相反.结论 miR-4677-3p通过靶向调控MMP 2 表达,进而调控ESCC细胞的增殖和迁移能力,该分子可能成为ESCC治疗的潜在靶点.
Objective To investigate the effect and molecular mechanism of miR-4677-3p-mediated targeting of matrix metalloproteinase-2(MMP2)on the proliferation and migration of esophageal squamous cell carcinoma(ESCC)cells in vitro.Methods The GSE263647 dataset was downloaded from the GEO database,and bioinformatic analysis identified MMP2 as a key prognosis-associated gene in ESCC.Potential miRNA regulating MMP2 expression were predicted using miRWalk and miRDB databases.MMP2 expression levels were examined by qRT-PCR and Western blot in human normal esophageal epithelial cells(HEEC)and four ESCC cell lines.MMP2 was knocked down by siRNA transfection and overexpressed via lentivirus infection in two ESCC cell lines(KYSE-150 and KYSE-70).Cell proliferation was assessed using the CCK-8 assay,and cell migration ability was observed via the scratch wound healing assay.Cells were transfected with miR-4677-3p mimics or inhibitor to evaluate MMP2 expression changes.Results 467 differentially expressed genes and 89 miRNAs were identified.MMP2 showed significantly elevated expression in ESCC tissues and cell lines,and its high expression was associated with poor patient prognosis.Functional analysis showed that MMP2 knockdown significantly inhibited cellular proliferation and migration in ESCC cells,while overexpression enhanced these malignant phenotypes.miR-4677-3p mimics downregulated MMP2 expression and suppressed proliferative and migratory capacities,whereas the inhibitor had the opposite effect.Conclusion miR-4677-3p modulates proliferation and migration of ESCC cells through targeted regulation of MMP2 expression,suggesting its potential as a therapeutic target for ESCC.
王新帅;陆佳;申深;张杰冲
河南科技大学临床医学院,河南科技大学第一附属医院,中国 洛阳,471003河南科技大学临床医学院,河南科技大学第一附属医院,中国 洛阳,471003河南科技大学临床医学院,河南科技大学第一附属医院,中国 洛阳,471003河南科技大学临床医学院,河南科技大学第一附属医院,中国 洛阳,471003
医药卫生
食管癌生物信息学MMP 2miR-4677-3p增殖迁移
esophageal cancerbioinformaticsMMP2miR-4677-3pproliferationmigration
《食管疾病》 2026 (1)
1-8,8
评论