The association of the expressions of MIR-122-5P and its target adam10 gene with human breast cancer

Nowadays, the causes of treatment failure in breast cancer known to be a genetically based disease comprises of the complex etiology of the disease, the fact that the molecular pathways have not yet been clarified and drug resistance. miRNAs having very important roles in the regulation of these pathways are negative regulators of genes encoding proteins. We believe that miR-122-5p, which is an oncogenic miRNA regulating translational efficiency or mRNA stability of ADAM10 gene, takes role in increasing of trastuzumab activity by suppressing ADAM10, that is, by preventing HER2/neu shedding, in breast cancer cells. Maybe, miR-122-5p may show its oncogenic features along many different pathways. We aimed to shed light on the pathophysiology of breast cancer by obtaining expression profile of miR-122-5p and its target, ADAM10 gene. By this way, we used Real-Time PCR to obtain expression profile of ADAM10 and miR-122-5p in breast cancer cell lines (MCF7, HCC1500, ZR-75-1, MDA-MB-231, SK-BR-3) and in mammary epithelial cell line (CRL-4010) as control and in tumor and non-tumor breast tissues, as control, of the breast cancer patients at the same time in the laboratory of our Department. According to expression results in SKBR3 which is our only HER2+ cell line responsive to trastuzumab, expression levels of ADAM10 and miR-122-5p were found significantly higher than in the control cell line. While the expression levels of miR-122-5p in other four cell lines were lower than in the control cell line, the ADAM10 expression levels in the same cell lines were found higher than in the control cell line. According to the expression profiles of ADAM10 and miR-122-5p, it is observed that there is a close relationship between these two with respect to the pathogenesis of breast cancer and this association is changing by the histopathology of the disease. Consequently, it could be said that miR-122-5p has a tumor suppressor role changing with the histopathologies or other characteristics of the breast cancer cells by targetting ADAM10 or upon other mechanisms and a comment about trastuzumab resistance could be made upon ADAM10 expression level in especially HER2+ breast cancer cells with the help of this effect of miR-122-5p. Key Words: miR-122-5p, ADAM10, breast cancer, trastuzumab, qRT-PCR