Comparative Study of the Effects of Docosahexaenoic Acid, Linoleic Acid, and Taxol in Decreasing the Expression of Mir-10B, and Mir-20A OncomiRs, and Their Target Major Histocompatibility Complex Class I Chain-Related Proteins A (MICA) in Triple-Negative Metastatic Breast Cancer Cell Line

Background: Molecular signatures of the effects of widely used omega-3 and omega-6 fatty acids as dietary supplements and even in cancer therapy have been studied. Of them, microRNAs, have been shown to undergo altered expression after treatment with docosahexaenoic acid (DHA) and linoleic acid (LA) in different cancer types. In this study, the expression level of two well-known onco-microRNAs (miR), miR-10b and miR-20a, and also major histocompatibility complex class I chain-related protein A (MICA) as the target for these oncomiRs were investigated after treatment with DHA, LA, and common therapeutic agent Taxol. Methods: MDA-MB-231 cells were cultured in a complete RPMI 1640 medium and an MTT assay was performed to determine IC50 of DHA, LA, and Taxol. Cells were treated by DHA (100µM), LA (50µM), and Taxol (0.3µM) alone or in different combinations. After RNA extraction and cDNA synthesis, the expression levels of miR-10b, miR-20a, and MICA were determined by quantitative real-time PCR. U6 and β-Actin were used as endogenous controls, respectively. Results: Our findings showed that DHA, LA, and Taxol, and their combinations led to the significantly decreased expression of miR-10b and miR-20a (all P<0.0001). The expression level of miR-10b and miR-20a significantly decreased when treated with the LA+TAX combination. MICA as the target of miR-10b and miR-20a was also down-regulated significantly (P<0.0001) especially when treated with DHA+LA+TAX. Conclusion: Useful effects of DHA, LA, and their combination in breast cancer (BC) could be interpreted in part by decreasing the expression level of oncomiRs. In the case of MICA have had some contrary. High expression of MICA/B caused an approving outcome concerning the relapse-free period in early BC patients, however; some studies have shown that higher MICA expression was found as a sign of poor prognosis in BC. The decreased expression of MICA in the present study suggests the potential role of DHA and LA should be used in dietary supplements of BC patients.