Molecular signaling pathway enrichment analyses of hsa-mir-548g targetome in order to decipher its precise molecular role as diagnostic biomarker in breast cancer

Breast cancer is the fourth common type of cancer among Iranian women. miRNAs are a class of non- coding RNAs which regulate genes expression post-transcriptionally. A single microRNA contemporaneously can control hundreds of genes as indicated by its targetome. Recent studies have shown that deregulation of hsa-miR-548g, is associated with different types of cancer such as breast,lung, and bladder cancer, nominating that as promising diagnostic biomarker. Although, most of recent studies have reported down-regulation of hsa-miR-548g in breast cancer, in several studies its up-regulation has been observed. These inconsistent observations have brought considerable controversies about precise role of hsa-miR-548g during pathogenesis of breast cancer and its potential as a diagnostic biomarker in this disaes. Here by using signaling pathway enrichment analyses, an attempt is made to decipher the precise role of hsa-miR-548g in breast cancer and examine its potential as diagnostic biomarker in this type of cancer. First, validated and predicted targets of hsa-miR-548g were retrieved form mirtarbase and mirwalk database, respectively. Next, Unigene database was used tocheck its approximate expression in breast tissue and breast malignancy. Finally, by imputing breast specific expressed targetome into DAVID database the most statistically relevant signaling pathwayswith hsa-miR-548g targetome in breast cancer were characterized. Our data revealed that some KEGG signaling pathway such as pathway incancer , p53 signaling pathway , cell cycle , MAPK signalingpathway , apoptosis and VEGF signaling pathway are the most relevant pathways with hsa-miR- 548g targetome. Interestingly, some proliferation/survival inducing proteins (such as CDK4/6, CyclinD1, Raf, PKB/AKT, FGF, MEK1 and VEGFR2) and also anti-apoptosis protein Bcl-2 were the most enriched genes in aforementioned pathways. Results clearly showed that hsa-miR-548g exert a tumor suppressor role in breast cancer at the molecular level. Therefore, its down-regulation observed in previous studies is more consistent with our data and could be considered as diagnostic biomarker inbreast cancer. However, more in vitro and in vivo studies are required to confirm our bioinformatics results.

کلیدواژه ها:

Breast Cancer ، Cancer Diagnosis ، Cancer Genetics ، Cancer Treatment and Management ، Targeted Cancer Therapy