Bioinformatic and experimental analyses of GATA3 and its regulatory miRNAs in breast Cancer

Abstract

Abstract Background GATA binding protein 3 (GATA3) is a transcription factor that plays a critical role in the differentiation and function of luminal epithelial cells in the breast. MicroRNAs (miRNAs) are small non-coding RNAs that modulate gene expression and their dysregulation has been implicated in cancer. The purpose of this study was to investigate the expression of GATA3 and its corresponding targeting miRNAs in breast cancer. Materials and methods In this study, we used bioinformatic tools, including the miRWalk database and RNA Hybrid online tool, to identify potential miRNAs that target the GATA3 mRNA. Then, we collected frozen tissue specimens from 67 breast cancer patients and 67 adjacent normal breast tissue samples and evaluated the expression levels of GATA3, hsa-miR-433-3p, and hsa-miR-144-3p using quantitative RT-PCR. Results We found that hsa-miR-433-3p and hsa-miR-144-3p are potential miRNAs that target the GATA3 mRNA, and we found that both were significantly downregulated in breast cancer tissues relative to adjacent normal breast tissues (P < 0.0001). We also observed a significant upregulation of the GATA3 mRNA in breast cancer tissues (P < 0.0001). Additionally, we found that their dysregulation was associated with clinicopathological features such as invasive carcinoma and carcinoma in situ subtypes, tumor grade, estrogen receptor status, progesterone receptor status, and HER2 status. Conclusions Our study represents the first attempt to investigate the expression of GATA3 and its targeting miRNAs simultaneously in breast cancer. Our findings suggest that dysregulation of these genes may contribute to breast cancer development and progression.

Keywords

• GATA3
• MiRWalk database
• RNA hybrid online tool
• hsa-miR-433-3p
• hsa-miR-144-3p