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

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 in vitro and in vivo 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.

Keywords: Wnt/β-catenin; endometrial carcinoma; epithelial-mesenchymal transition; microRNA-15a-5p; vascular endothelial growth factor A.