MicroRNA‑4712‑5p promotes proliferation of the vulvar squamous cell carcinoma cell line A431 by targeting PTEN through the AKT/cyclin D1 signaling pathways

Abstract

The aim of the present study was to screen differentially expressed miRNAs in vulvar squamous cell carcinoma (VSCC), observe the role of microRNA-4712-5p in VSCC and investigate its targets and regulatory mechanism. Differentially expressed miRNAs in human VSCC tissues were screened. microRNA-4712-5p was selected and its expression level was verified in clinical tissue samples and the VSCC cell line A431 by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. The overexpression vector of microRNA-4712-5p was prepared and transfected into A431 cells; subsequently, cell invasion and metastasis were examined by Cell Counting Kit-8 and Transwell migration assays. Furthermore, the target gene of miRNA-4712-5p was predicted by bioinformatics and verified by The Dual-Luciferase® Reporter (DLR™) Assay System. The expression of phosphatase and tensin homologue (PTEN) and its downstream proteins, such as protein kinase B (PKB; AKT), glycogen synthase kinase (GSK)3β and cyclin D1, were detected by western blot assays. The expression level of microRNA-4712-5p in VSCC tissues and the A431 cell line was found to be significantly increased, promoting proliferation and invasion of VSCC. The DLR™ assay indicated that PTEN was a target of miR-4712-5p. RT-qPCR revealed that PTEN expression was markedly lower in VSCC tissues compared with that in adjacent tissues. After A431 cells were transfected with the miRNA-4712-5p overexpression vector, phospho-AKT (p-AKT) and cyclin D1 expression were notably increased, but miRNA-4712-5p-targeted PTEN and phospho-GSK3β (p-GSK3β) protein markedly decreased. Therefore, microRNA-4712-5p can reduce the expression of PTEN, further affecting its downstream p-AKT, p-GSK3β and cyclin D1 signaling pathways, promoting the proliferation and invasion of VSCC.

Could MicroRNAs Be Useful Tools to Improve the Diagnosis and Treatment of Rare Gynecological Cancers? A Brief Overview

“…Several miRNAs that are overexpressed in RGCs have been shown to have oncogenic roles in vitro, as well as defined molecular targets that they regulate ( Table 3 ). miR-9 [ 55 ], miR-10a [ 73 ], miR-21 [ 126 ], miR-590-5p [ 108 ], miR-3147 [ 110 ] and miR-4712 [ 109 ] have been described as “oncomiRs” across multiple mammalian cell types, which is consistent with their role in RGCs. In addition, underexpressed miRNAs in RGCs such as miR-34 [ 124 ], miR-126 [ 72 ] and miR-196b [ 125 ] act as tumor suppressors.…”

“…Finally, upregulation of miR-590-5p may promote cellular malignant behavior via the target gene TGFβR II . In another study, there was an increased level of expression of miRNA-4712-5p in VSCC, promoting proliferation and invasion, by affecting PTEN and its downstream p-GSK3β, p-AKT, and cyclin D1 signaling pathways [ 109 ]. It has also been shown that miR-3147 serves as an oncomiR in VSCC via suppression of Smad4 [ 110 ].…”

“…6.1.6. miR-4712-5p Regulates PTEN and Affects Its Downstream p-AKT, p-GSK3β and Cyclin D1 Signaling Pathways Yang et al [109] investigated the role of miR-4712-5p and its regulatory mechanism in VSCC, and found increased levels of miR-4712-5p both in VSCC tissues and the A431 cell line. Moreover, miR-4712-5p overexpression promotes proliferation and invasion of VSCC cells.…”

MicroRNAs as Potential Biomarkers in Gynecological Cancers

“…Overexpression of miR-4712-5p affects invasion and cell proliferation in vulvar squamous cell carcinoma. In addition, it targets PTEN, reducing its expression, and may affect the PTEN/AKT/p-GSK3β/cyclin D1 signaling pathway, affecting cell proliferation [ 142 ].…”

miR-129-5p Plays an Anticancer Role in Colon Cancer by Targeting RSF1

“…Targeted therapy is the product of the times with the development of society and science and technology, which is forward-looking (23). Targeted therapy is a molecule-based therapy, which is different from the previous methods of surgery, radiotherapy and chemotherapy based on the cellular and molecular level and through specific oncogenic sites (24). Medical scientists have gradually deepened their understanding of cancer from the parenchymal lesions to cells to the molecular level, and a relatively new and less painful way of targeted therapy has emerged (25).…”