MicroRNA‑195 inhibits epithelial‑mesenchymal transition by targeting G protein‑coupled estrogen receptor 1 in endometrial carcinoma

Abstract

Epithelial-mesenchymal transition (EMT) has been shown to exert promoting effects on the progression of a number of cancer types, including endometrial carcinoma (EC). MicroRNA (miRNA or miR)-195 has been shown to function as a tumor suppressor. This study aimed to explore the potential role of miR-195 in the EMT process of EC. miR-195 overexpression (Mimics) and mimics control (Mock) vectors were constructed and transfected into human endometrial cancer cells (AN3-CA and Hec1A) using Lipofectamine 2000, and cell viability was detected using the Cell Counting kit-8 (CCK-8). The invasive and migratory capacities of the cells transfected with the Mimics or Mock vectors were assessed by Transwell and wound healing assays. Relative mRNA and protein levels were analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. Using TargetScan prediction, the potential target of miR-195 was identified and was further verified by dual-luciferase reporter assay. Following transfection with miR-195 mimics, the viability of the AN3-CA and Hec1A cells decreased in a time-dependent manner, specifically at 24 h. The wound closure rate and the number of invaded cells in the Mimics group were much lower than those in the Control and Mock groups (P<0.01). miR-195 overexpression significantly upregulated the mRNA and protein levels of tissue inhibitor of metalloproteinase 2 (TIMP-2), while it downregulated the expression levels of matrix metalloproteinase (MMP)-2 and MMP-9. Moreover, the phosphorylation levels of PI3K and AKT were also notably decreased (P<0.01). G protein-coupled estrogen receptor 1 (GPER) was identified as a target of miR-195. On the whole, the findings of this study indicate that the inhibitory effects of miR195 on EC cell migration and invasion are associated with the PI3K/AKT signaling pathway and GPER expression.

Expression and Role of the G Protein-Coupled Estrogen Receptor (GPR30/GPER) in the Development and Immune Response in Female Reproductive Cancers

“…It has also been described that E2, G-1, OHT, IGF-1, and insulin favor the increased expression of GPER at mRNA and protein levels (35,(40)(41)(42). Several studies have reported that direct stimulation with E2, G-1, and OHT increases the carcinogenic characteristics of EC cell lines, such as proliferation, migration, and invasion, involving mechanisms such as activation of signaling pathways like MAPK and PI3K, calcium influx via Cav1.3 and DAKα, phosphorylation of FAK, and increased production of MMP-2/9, c-Fos, and cyclin D1 (33,35,40,41,(43)(44)(45)(46)(47)(48)(49)(50). However, only one report showed the inhibition of proliferation in RL95-2 and HEC-1A cell lines stimulated with G-1 in a dose-dependent manner (37).…”

“…However, only one report showed the inhibition of proliferation in RL95-2 and HEC-1A cell lines stimulated with G-1 in a dose-dependent manner ( 37 ). Also, miR-195 controls GPER expression in vitro in AN3-CA and HEC-1A cells ( 44 ).…”

MicroRNA as Epigenetic Modifiers in Endometrial Cancer: A Systematic Review

“…This systematic review identified 105 original articles and two literature reviews reporting the expression pattern of miRNAs [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 ,…”

<p>Long Noncoding RNA SNHG12 Indicates the Prognosis and Accelerates Tumorigenesis of Diffuse Large B-Cell Lymphoma Through Sponging microR-195</p>

“…27 Moreover, miR-195 could suppress the progression of prostate cancer, lung adenocarcinoma and endometrial carcinoma. [28][29][30] A study reported that LINC00355 can sponge miR-195, which inhibits apoptosis promotes the progression of head and neck squamous cell carcinoma. 31 Wu et al demonstrated that BRAF-activated noncoding RNA promotes tumorigenesis of pancreatic cancer by sponging miR-195.…”