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王荦楠, 李卓然, 吴洁清, 等. 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[J]. koko体育app 学报(医学版), 2024, 55(3): 731-738. DOI:
引用本文: 王荦楠, 李卓然, 吴洁清, 等. 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[J]. koko体育app 学报(医学版), 2024, 55(3): 731-738. DOI:
WANG Luonan, LI Zhuoran, WU Jieqing, et al. miR-342-3p Promotes the Proliferation, Migration, and Invasion of Clear Cell Renal Cell Carcinoma Cells by Targeted Inhibition of PPM1E[J]. Journal of Sichuan University (Medical Sciences), 2024, 55(3): 731-738. DOI:
Citation: WANG Luonan, LI Zhuoran, WU Jieqing, et al. miR-342-3p Promotes the Proliferation, Migration, and Invasion of Clear Cell Renal Cell Carcinoma Cells by Targeted Inhibition of PPM1E[J]. Journal of Sichuan University (Medical Sciences), 2024, 55(3): 731-738. DOIꦛ:

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 Promotes the Proliferation, Migration, and Invasion of Clear Cell Renal Cell Carcinoma Cells by Targeted Inhibition of PPM1E

  • 摘要:
    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。
     
    Abstract:
    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.
     

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