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[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].

作者信息

Wang Luonan, Li Zhuoran, Wu Jieqing, Xie Jinling

机构信息

( 453100) The First Ward, Department of Oncology, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, China.

出版信息

Sichuan Da Xue Xue Bao Yi Xue Ban. 2024 May 20;55(3):731-738. doi: 10.12182/20240560403.

DOI:10.12182/20240560403
PMID:38948282
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11211793/
Abstract

OBJECTIVE

To explore the effects of microRNA-342-3p/MgMn-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 was verified by dual-luciferase reporter gene assay. The cells were transfected with miR-342-3p mimic and pcDNA- 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 (<0.05). The overall survival in the miR-342-3p high-expression group was significantly shorter than that in the low-expression group (<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 (<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 mRNA (<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 (<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 (<0.05). However, PPM1E could reverse the promotion effect of miR-342-3p mimic on ccRCC cells (<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.

摘要

目的

探讨微小RNA-342-3p/镁锰依赖性蛋白磷酸酶1E(miR-342-3p/PPM1E)对透明细胞肾细胞癌(ccRCC)细胞增殖、迁移和侵袭的影响。

方法

检索基因芯片GSE12105、GSE23085、GSE66271和GSE66270,分析miR-342-3p、PPM1E与ccRCC临床恶性表型之间的关系。用miR-342-3p抑制剂转染ACHN和769-P细胞。检测miR-342-3p对细胞增殖、迁移和侵袭的影响。构建miR-342-3p稳定高表达的ACHN细胞系,观察该细胞系在BALB/c裸鼠中的致瘤性。通过双荧光素酶报告基因实验验证miR-342-3p与[此处原文缺失相关内容]的靶向关系。用miR-342-3p模拟物和pcDNA-质粒转染细胞,观察PPM1E是否能逆转miR-342-3p过表达对细胞增殖、迁移和侵袭的影响。

结果

ccRCC中miR-342-3p表达上调,不同T分期、G分期肿瘤患者及不同预后患者之间存在显著差异(<0.05)。miR-342-3p高表达组的总生存期明显短于低表达组(<0.05)。与miR-NC组相比,抑制剂组miR-342-3p水平显著下调,细胞增殖能力以及迁移和侵袭细胞数量也显著减少(<0.05)。与miR-NC组相比,miR-342-3p组肿瘤组织体积和质量以及miR-342-3p水平显著增加,但[此处原文缺失相关内容]mRNA水平显著降低(<0.05)。ccRCC中PPM1E表达下调,不同M分期、N分期、G分期肿瘤患者及不同复发状态之间存在显著差异(<0.05)。miR-342-3p可靶向抑制PPM1E的表达。与miR-NC组相比,miR-342-3p组细胞增殖能力显著增强且迁移和侵袭细胞数量增加(<0.05)。然而,PPM1E可逆转miR-342-3p模拟物对ccRCC细胞的促进作用(<0.05)。

结论

miR-342-3p可靶向抑制PPM1E表达,从而促进ccRCC细胞的增殖、迁移和侵袭。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa0/11211793/0d4e3f3b5272/scdxxbyxb-55-3-731-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa0/11211793/d90071f31927/scdxxbyxb-55-3-731-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa0/11211793/c2bd4675b78c/scdxxbyxb-55-3-731-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa0/11211793/0c58912e6f56/scdxxbyxb-55-3-731-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa0/11211793/91176f7ddea2/scdxxbyxb-55-3-731-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa0/11211793/0d4e3f3b5272/scdxxbyxb-55-3-731-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa0/11211793/d90071f31927/scdxxbyxb-55-3-731-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa0/11211793/c2bd4675b78c/scdxxbyxb-55-3-731-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa0/11211793/0c58912e6f56/scdxxbyxb-55-3-731-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa0/11211793/91176f7ddea2/scdxxbyxb-55-3-731-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa0/11211793/0d4e3f3b5272/scdxxbyxb-55-3-731-5.jpg

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