miR-155-5p 通过靶向 PEG3 促进透明细胞肾细胞癌的细胞增殖和迁移。

miR-155-5p Promotes Cell Proliferation and Migration of Clear Cell Renal Cell Carcinoma by Targeting PEG3.

机构信息

Department of Urology Surgery, Jinhua Hospital of Zhejiang University, Jinhua, China.

出版信息

Urol Int. 2021;105(9-10):906-915. doi: 10.1159/000514416. Epub 2021 Jun 30.

DOI:10.1159/000514416

PMID:34192708

Abstract

OBJECTIVE

miR-155-5p as an important microRNA has been extensively studied for its biological functions and mechanisms in various cancers. However, the role and underlying mechanisms in clear cell renal cell carcinoma (ccRCC) remain to be further elucidated.

METHODS

Bioinformatics methods were implemented to analyze differentially expressed genes in the cancer genome atlas database. qRT-PCR and Western blot were employed to detect the expression of miR-155-5p and paternally expressed gene 3 (PEG3) mRNA as well as protein expression. Cell lines with miR-155-5p knockdown or miR-155-5p/PEG3 co-overexpression were constructed. A series of experiments including the MTT method, wound healing assay, and transwell assay were carried out to detect the proliferation, migration, and invasion of cancer cells in different treatment groups. Bioinformatics analysis and dual-luciferase assay were conducted to confirm the targeting relationship between PEG3 and miR-155-5p in ccRCC.

RESULTS

miR-155-5p was found to be significantly upregulated in ccRCC cells, while PEG3 exhibited significantly low expression. The downregulation of miR-155-5p could inhibit cell proliferation, migration, and invasion of ccRCC. miR-155-5p could inhibit the expression of PEG3. The overexpression of miR-155-5p could promote cell proliferation, migration, and invasion, whereas overexpression of PEG3 could significantly attenuate such effect. Therefore, miR-155-5p may promote cell growth of ccRCC via inhibiting PEG3 expression.

CONCLUSION

These findings validated the effect of miR-155-5p/PEG3 on ccRCC cells and provided novel potential targets for the prognosis and treatment of patients with ccRCC.

摘要

目的

miR-155-5p 作为一种重要的 microRNA，其在各种癌症中的生物学功能和机制已得到广泛研究。然而，其在透明细胞肾细胞癌（ccRCC）中的作用和潜在机制仍有待进一步阐明。

方法

采用生物信息学方法分析癌症基因组图谱数据库中差异表达的基因。采用 qRT-PCR 和 Western blot 检测 miR-155-5p 和父系表达基因 3（PEG3）mRNA 及蛋白表达。构建 miR-155-5p 敲低或 miR-155-5p/PEG3 共过表达的细胞系。通过 MTT 法、划痕愈合实验和 Transwell 实验等一系列实验检测不同处理组癌细胞的增殖、迁移和侵袭能力。通过生物信息学分析和双荧光素酶报告基因实验验证 PEG3 在 ccRCC 中与 miR-155-5p 的靶向关系。

结果

miR-155-5p 在 ccRCC 细胞中表达显著上调，而 PEG3 表达显著下调。miR-155-5p 的下调可抑制 ccRCC 细胞的增殖、迁移和侵袭。miR-155-5p 可抑制 PEG3 的表达。miR-155-5p 的过表达可促进 ccRCC 细胞的增殖、迁移和侵袭，而过表达 PEG3 可显著减弱这种作用。因此，miR-155-5p 可能通过抑制 PEG3 表达促进 ccRCC 细胞的生长。