Circulating Micro RNA 181A as Biomarker in Breast Cancer, Its Possible Association with Metastasis & Epithelial Mesenchymal Transformation

Abstract

Background: Recent studies have reported the involvement of micro RNA 181a in diverse cellular functions. Though some studies have shown that miR-181a expression is downregulated in several human solid tumors, others have demonstrated that upregulation of miR-181a may promote metastasis and invasion of human cancers. Aim of the Study: The aim of this work is to detect the level of circulating miRNA-181a in breast cancer cases at different stages and to study its role in metastasis & epithelial mesenchymal transformation (EMT) through the possible association between miRNA 181a and transforming growth factor beta (TGFβ) signaling pathway. Subjects and Methods: The present work included 70 female patients, with breast cancer at different stages 30 patients with metastatic disease and 40 patients with non-metastatic disease 20 healthy subjects were taken as a control group. We detected miRNA-181a expression in peripheral blood with qRT PCR, and TGF-beta, SMAD-4, SNAIL-1 and Bim expression by quantitative PCR. Results: miRNA-181a, TGF-beta, SNAIL-1 and SMAD-4 were significantly upregulated in patients with metastatic breast cancer compared to patients with non-metastatic disease while Bim is significantly downregulated in metastatic versus non-metastatic group. Also, miRNA-181a was a prognostic marker for disease progression and overall survival. Conclusion: signaling pathway of TGFβ-SMAD, regulate miRNA-181a which in turn play role in stabilizing SNAIL transcription factor that promote tumor aggressiveness and metastasis through epithelial mesenchymal transition, as well as down-regulation of Bim.