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微小RNA-15a-5p通过下调血管内皮生长因子A(VEGFA)并抑制Wnt/β-连环蛋白信号通路来抑制子宫内膜癌的增殖、侵袭和迁移。

MicroRNA-15a-5p inhibits endometrial carcinoma proliferation, invasion and migration via downregulation of VEGFA and inhibition of the Wnt/β-catenin signaling pathway.

作者信息

Wang Honggang, Yang Qingju, Li Jieping, Chen Wenping, Jin Xiao, Wang Yaowen

机构信息

Department of Clinical Laboratory, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China.

Department of Gynaecology, Linyi People's Hospital, Dezhou, Shandong 251500, P.R. China.

出版信息

Oncol Lett. 2021 Apr;21(4):310. doi: 10.3892/ol.2021.12570. Epub 2021 Feb 22.

Abstract

Endometrial carcinoma (EC) is one of the most common malignant gynecological tumors. Dysregulation of microRNAs (miRNAs/miRs) is frequently identified in human tumors, playing key regulatory roles in tumor growth and metastasis. The present study aimed to explore the functions and potential mechanisms of miR-15a-5p in EC progression. RT-qPCR was used to detect the expression levels of miR-15a-5p and vascular endothelial growth factor A (VEGFA) mRNA. Western blot analysis was performed to examine the expression of related proteins. Functional assays, including proliferation and Transwell assays were performed to determine the roles of miR-15a-5p in EC progression. TargetScan and luciferase reporter assays were used to explore the potential target genes of miR-15a-5p. The results revealed that miR-15a-5p was underexpressed in EC tissue samples in comparison with that in matched normal tissue samples. The expression level of miR-15a-5p was associated with the clinicopathologic characteristics of EC patients. Notably, both and assays revealed that miR-15a-5p upregulation significantly inhibited EC growth and metastasis. Furthermore, bioinformatics analysis and dual luciferase reporter assay indicated that VEGFA was a candidate target of miR-15a-5p. Mechanistic investigation revealed that miR-15a-5p inhibited EC development via regulation of Wnt/β-catenin pathway and targeting of VEGFA. In summary, the present results demonstrated that miR-15a-5p could inhibit EC development and may serve as a promising therapeutic biomarker in EC.

摘要

子宫内膜癌(EC)是最常见的妇科恶性肿瘤之一。微小RNA(miRNA/miR)失调在人类肿瘤中经常被发现,在肿瘤生长和转移中发挥关键调节作用。本研究旨在探讨miR-15a-5p在EC进展中的功能及潜在机制。采用RT-qPCR检测miR-15a-5p和血管内皮生长因子A(VEGFA)mRNA的表达水平。进行蛋白质印迹分析以检测相关蛋白的表达。进行包括增殖和Transwell实验在内的功能实验,以确定miR-15a-5p在EC进展中的作用。使用TargetScan和荧光素酶报告基因实验来探索miR-15a-5p的潜在靶基因。结果显示,与配对的正常组织样本相比,miR-15a-5p在EC组织样本中表达下调。miR-15a-5p的表达水平与EC患者的临床病理特征相关。值得注意的是,增殖实验和Transwell实验均显示,miR-15a-5p上调显著抑制EC的生长和转移。此外,生物信息学分析和双荧光素酶报告基因实验表明,VEGFA是miR-15a-5p的候选靶标。机制研究表明,miR-15a-5p通过调节Wnt/β-连环蛋白通路和靶向VEGFA抑制EC的发展。综上所述,本研究结果表明,miR-15a-5p可抑制EC的发展,并可能成为EC中有前景的治疗生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c385/7905532/87963efcdbcf/ol-21-04-12570-g00.jpg

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