首页|miR-342-3p通过靶向抑制PPM1E促进肾透明细胞癌细胞的增殖、迁移和侵袭

miR-342-3p通过靶向抑制PPM1E促进肾透明细胞癌细胞的增殖、迁移和侵袭

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目的 探究微小RNA-342-3p/Mg2+Mn2+依赖的蛋白磷酸酶1E(miR-342-3p/PPM1E)轴对肾透明细胞癌(clear cell renal cell carcinoma,ccRCC)细胞增殖、迁移和侵袭的影响.方法 搜索基因芯片GSE12105、GSE23085、GSE66271及GSE66270,分析miR-342-3p、PPM1E与ccRCC临床恶性表型的关系.miR-342-3p inhibitor转染ACHN、769-P细胞,检测miR-342-3p对细胞增殖、迁移和侵袭的影响;构建稳定高表达miR-342-3p的ACHN细胞系,并观察其在Balb/c裸鼠体内的成瘤情况;双萤光素酶报告基因验证miR-342-3p与PPM1E的靶向关系,同时转染miR-342-3p mimic、pcDNA-PPM1E质粒,观察PPM1E是否可逆转miR-342-3p过表达对细胞增殖、迁移和侵袭的影响.结果 miR-342-3p在ccRCC中表达上调,且在不同T分期、G分期、预后患者中存在差异表达(P<0.05);miR-342-3p高表达组总生存期明显低于miR-342-3p低表达组(P<0.05).与miR-NC组相比较,inhibitor组miR-342-3p水平显著下调,细胞增殖能力、迁移细胞数和侵袭细胞数显著降低(P<0.05);与miR-NC组相比较,miR-342-3p组肿瘤组织体积及质量、miR-342-3p水平均明显升高,PPM1E mRNA水平明显降低(P<0.05).PPM1E在ccRCC中表达下调,在不同M分期、N分期、G分期及复发情况患者中存在差异表达(P<0.05).miR-342-3p可靶向抑制PPM1E表达,与miR-NC组相比较,miR-342-3p组细胞增殖能力、迁移细胞数和侵袭细胞数明显升高(P<0.05),而PPM1E可逆转miR-342-3p mimic对ccRCC细胞的促进作用(P<0.05).结论 miR-342-3p可靶向抑制PPM1E表达,从而促进ccRCC细胞增殖、迁移和侵袭.
miR-342-3p Promotes the Proliferation,Migration,and Invasion of Clear Cell Renal Cell Carcinoma Cells by Targeted Inhibition of PPM1E
Objective To explore the effects of microRNA-342-3p/Mg2+Mn2+-dependent protein phosphatase 1E(miR-342-3p/PPM1E)on the proliferation,migration,and invasion of clear cell renal cell carcinoma(ccRCC)cells.Methods The gene chips GSE12105,GSE23085,GSE66271,and GSE66270 were searched,and the relationship between miR-342-3p,PPM1E,and the clinical malignant phenotypes of ccRCC was analyzed.ACHN and 769-P cells were transfected with miR-342-3p inhibitor.The effects of miR-342-3p on cell proliferation,migration,and invasion were examined.ACHN cell line with stable and high expression of miR-342-3p was constructed,and the tumorigenicity of the cell line in BALB/c nude mice was observed.The targeted relationship between miR-342-3p and PPM1E was verified by dual-luciferase reporter gene assay.The cells were transfected with miR-342-3p mimic and pcDNA-PPM1E plasmids to observe whether PPM1E could reverse the effects of miR-342-3p overexpression on the proliferation,migration,and invasion of the cells.Results The expression of miR-342-3p was upregulated in ccRCC,and there were significant differences among patients with tumors of different T stages and G stages and those with different prognoses(P<0.05).The overall survival in the miR-342-3p high-expression group was significantly shorter than that in the low-expression group(P<0.05).Compared with those in the miR-NC group,the miR-342-3p level was significantly downregulated in the inhibitor group,and the cell proliferation ability and the numbers of migrating and invading cells were also significantly decreased(P<0.05).Compared with the miR-NC group,miR-342-3p group had significantly increased volume and mass of tumor tissues and miR-342-3p level,but significantly decreased level of PPM1E mRNA(P<0.05).The expression of PPM1E was downregulated in ccRCC,and there were significant differences among patients with tumors of different M stages,N stages,and G stages,and different recurrence statuses(P<0.05).The miR-342-3p could inhibit the expression of PPM1E in a targeted way.Compared with the miR-NC group,the miR-342-3p group had significantly increased cell proliferation ability and increased numbers of migrating and invading cells(P<0.05).However,PPM1E could reverse the promotion effect of miR-342-3p mimic on ccRCC cells(P<0.05).Conclusion The miR-342-3p can inhibit PPM1E expression in a targeted way,and thus promotes the proliferation,migration,and invasion of ccRCC cells.

Clear cell renal cell carcinomamiR-342-3pMg2+Mn2+-dependent protein phosphatase 1EProliferationMigrationInvasion

王荦楠、李卓然、吴洁清、谢晋玲

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新乡医学院第一附属医院 肿瘤内科一病区 (新乡 453100)

肾透明细胞癌 miR-342-3p Mg2+Mn2+依赖的蛋白磷酸酶1E 增殖 迁移 侵袭

河南省医学科技攻关计划联合共建项目(2022)

LHGJ2022062

2024

四川大学学报(医学版)
四川大学

四川大学学报(医学版)

CSTPCD北大核心
影响因子:0.961
ISSN:1672-173X
年,卷(期):2024.55(3)