The prognostic value of vitamin D receptor and its up-stream miR-27b and miR-125a expression in breast cancer patients

Abstract

Breast cancer is a heterogeneous disease that is conventionally classified according to histology and immunopathology. An updated classification of breast cancer is dependent upon messenger RNA (mRNA) expression profiling, and micro-RNA (miRNA) expression signature due to their role in regulating malignant progression. The aim of this study was to investigate the expression patterns of VDR and aromatase genes expression in malignant breast cancer tissues in comparison with the adjacent normal tissues together with the expression pattern of two micro RNAs (miR-27b and 125a) as an upstream factors that regulate the stability of VDR mRNA as tumor suppressors. The present study was carried out on 50 female breast cancer patients (30 postmenopausal, 20 premenopausal). Breast tissues were used for total RNA isolation from malignant breast tissue and adjacent normal breast tissues, gene expression analysis of VDR and aromatase in breast tissues at mRNA using RT-PCR, gene expression analysis of miR-27b, miR-125a using RT-PCR. The gene expression of VDR is up-regulated in the malignant breast tissues compared to adjacent normal tissues and controlled by the expression of miR-125a and miR-27b. The tumor suppressor miR-125a was downregulated in breast malignant tissues. VDR gene expression is affected by aromatase gene expression which showed up-regulation in malignant breast tissues. The crosstalk between VDR and miR-125a, miR27b and aromatase may determine the subset of patients that could be responsive to adjuvant treatment with vitamin D agonist. According to the results of VDR expression and other parameters, postmenopausal patients may be more sensitive to vitamin D therapy than premenopausal patients.