Endometrial cancer is the fourth most common malignancy of the female genital tract worldwide [
1], and the major histological type of endometrial cancer is endometrial endometrioid adenocarcinoma (EEC) [
2]. Although the integrated diagnosis and treatment provide significant insights into EEC, it still has some limitations including disease biology, morbidity and mortality. Therefore, a better understanding of the molecular mechanism of EEC maybe helpful to develop more effective therapies for the treatment of this disease.
Epithelial-to-mesenchymal transition (EMT) is a well-known mechanism for invasion (or metastasis) for many types of cancer [
3]. It is a process during which tumor cells with epithelial characteristics lose their differentiated phenotypes and change their morphology to those characteristic of mesenchymal cells and migrate to the extracellular matrix [
4]. During EMT, the epithelial markers of tumor cells were lost, such as E-cadherin and certain cytokeratins. Whereas, tumor cells gain mesenchymal markers such as vimentin and fibronectin [
5]. EMT program plays important roles in promoting tumor cell invasion and chemoresistance of endometrioid adenocarcinoma cells via several transcription factors and related pathways, such as SNAIL (SNAI1), and SLUG (SNAI2) [
6]. It was reported that SLUG expression serves as a prognostic factor in EEC [
7]. In addition, one of the crucial signaling pathways of EMT in the pathogenesis of cancer is the transforming growth factor-beta/mothers against decapentaplegic homolog (TGF-β/SMAD) signaling pathway. The disturbances of the TGF-β pathway and overexpression or upregulation of SMAD4 expression were found to be important to the infiltration of the type I EEC [
8]. However, loss of SMAD4 protein expression occurs infrequently in EEC [
9]. SMAD3 is another member of the Smad proteins, which mediates the signals from the TGF-β superfamily ligands that regulate cell proliferation, differentiation and death [
10]. Based on its essential role in TGF-β signaling pathway, SMAD3 is related with tumor growth in cancer development. It was reported upregulated SMAD3 promotes EMT and predicts poor prognosis in pancreatic ductal adenocarcinoma [
11]. Therefore, EMT status maybe a molecular target in EEC.
A microRNA (miRNA) is a small non-coding RNA molecule (containing about 22 nucleotides) found in plants, animals, and some viruses, which functions in post-transcriptional regulation of gene expression [
12]. So far, several studies showed the miRNA-dependent posttranscriptional regulation of genes associated with EEC development [
13,
14]. Also EMT can be controlled by a specific set of miRNA. In the present study, due to the important role of EMT in EEC, we analyze all miRNAs expression profile of EEC in order to search for EMT-related miRNAs and investigate their role in EEC. Using an unbiased miRNA screen, we identified miR-23a as an down-regulated miRNA in EC. Through in silico prediction and luciferase reporterassay, we found that SMAD3, may be one of miR-23a target genes in EEC. Thus, we demonstrate that miR-23a might be as an EMT-related miRNA in EEC by targeting SMAD3.