Roohy Fatemeh, Moghanibashi Mehdi, Tahmasebi Sedigheh
Department of Biology, Faculty of Basic Sciences, Kazerun Branch, Islamic Azad University, Kazerun, Iran.
Department of Genetics, Faculty of Basic Sciences, Kazerun Branch, Islamic Azad University, Kazerun, P.O. Box: 73135-168, Iran.
Discov Oncol. 2024 Oct 24;15(1):588. doi: 10.1007/s12672-024-01479-y.
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.
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.
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.
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.
GATA结合蛋白3（GATA3）是一种转录因子，在乳腺腔上皮细胞的分化和功能中起关键作用。微小RNA（miRNA）是调节基因表达的小非编码RNA，其失调与癌症有关。本研究的目的是调查GATA3及其相应靶向miRNA在乳腺癌中的表达。
在本研究中，我们使用了生物信息学工具，包括miRWalk数据库和在线RNA Hybrid工具，来识别靶向GATA3 mRNA的潜在miRNA。然后，我们收集了67例乳腺癌患者的冷冻组织标本和67例相邻正常乳腺组织样本，并使用定量RT-PCR评估GATA3、hsa-miR-433-3p和hsa-miR-144-3p的表达水平。
我们发现hsa-miR-433-3p和hsa-miR-144-3p是靶向GATA3 mRNA的潜在miRNA，并且我们发现相对于相邻正常乳腺组织，这两种miRNA在乳腺癌组织中均显著下调（P < 0.0001）。我们还观察到乳腺癌组织中GATA3 mRNA显著上调（P < 0.0001）。此外，我们发现它们的失调与临床病理特征有关，如浸润性癌和原位癌亚型、肿瘤分级、雌激素受体状态、孕激素受体状态和HER2状态。
我们的研究首次尝试在乳腺癌中同时研究GATA3及其靶向miRNA的表达。我们的研究结果表明，这些基因的失调可能有助于乳腺癌的发生和发展。
