MicroRNAs 7/17/155 As A Potential Breast Tumor Stemness miRNA Cluster: Detection of Breast Cancer Grade Specific miRNA-mRNA Interaction Network Inspiration from Mammary Gland Development

Abstract: Background The process of breast tumor dedifferentiation is complex and unclear. The mechanism represents the origin of the genesis and development of high-grade breast stem cells. It seems that microRNAs have crucial regulatory functions in this complicated phenomenon. The main objective of this study is to identify a potential "breast tumor stemness miRNA cluster" using an in silico strategy and qRT-PCR validation guided by the molecular pattern of mammary gland development (MGD). Methods Microarray databases GEO and ArrayExpress were used to determine mRNA and microRNA expression in different grades of breast carcinoma (BC). Differential gene expression of mRNA (GSE29044) and miRNA (GSE4566) in three grades of BC was analyzed using GEO2R compared with normal tissue. The enrichment results revealed MGD -associated mechanisms and target mRNAs. Using the BC database, the interaction between target mRNAs and significantly altered miRNAs (PV ≤ 0.05) in each BC grade was found by miRNet. After confirming our results using the GSE26659 data, the expression of the target miRNAs in tissue samples (24 BC, 17 normal tissues) was examined by real-time PCR. miRwalk and the STRING database discovered the miRNAs of interest and mRNA networks. Results The MGD stages of puberty, pregnancy and lactation, and mammary gland epithelial development were significantly involved in the upregulated genes of GI and GII tumors. No significant upregulated MGD mechanisms were detected in GIII BC. In silico analysis revealed that miRs 7/17/155 had an upregulation pattern and miR-26a had a downregulation pattern. qPCR showed that the miRNAs 7/17/155 were significantly upregulated in GIII tumors (PV ≤ 0.05), while there were no notable changes in miR-26a. EGFR was the central node regulated by the miR 7/17/155 intermediate mRNA cluster. Conclusions Our results suggest that microRNAs 7/17/155 may be a potential cluster associated with formation of breast tumor stemness. This cluster can be used for the breast cancer dedifferentiation therapy or molecular classification of mammary tumor differentiation status.