Expression of Bioinformatically Candidate miRNAs including, miR-205-5p, and target gene (HER3/SMAD4/PTEN), Targeting PI3K/AKT Pathway in Triple-Negative Breast Cancer
Expression of Bioinformatically Candidate miRNAs including, miR-205-5p, and target gene (HER3/SMAD4/PTEN), Targeting PI3K/AKT Pathway in Triple-Negative Breast Cancer
Introduction: Triple-negative breast cancer (TNBC) is an invasive and lethal
form of breast cancer. PI3K pathway, which often activated in TNBC patients,
can be a target of miRNAs. The purpose of this study was bioinformatic
prediction of miRNAs targeting the key genes of this pathway and evaluation of
the expression of them and their targets in TNBC.
Methods: We predicted miRNAs targeting PIK3CA and AKT1
genes using bioinformatics tools. Extraction of total RNA, synthesis of cDNA
and quantitative real-time polymerase chain reaction were performed from 22
TNBC samples and normal adjacent tissues of breast
Results: Our results demonstrated that miR-205-5p were predicted to target
HER3, SMAD4, PTEN and three of mRNAs in PI3K/AKT signaling pathway,
respectively and were down-regulated while their target mRNAs were upregulated in clinical samples and cell lines. The analysis of the receiver
operating characteristic curve was done for the evaluation of the diagnostic
value of predicted miRNAs in TNBC patients
Conclusion: The findings of our studies showed that Mir-205-5p expression is
associated with direct and indirect effects on its target genes (PTEN, SMAD4,
HER3) in the tissue of breast cancer patients compared to controlling expression
reduction or expression silencing , and leads to the activation of the signaling
pathway towards cancer. It is likely that by modulating the HER3 gene, Mir 205
will also be regulated.
Keywords: Triple Negative Breast Cancer; MicroRNA; HER3; PTEN; SMAD4 ؛Bioinformatics