Received: 14 August 2017 | Accepted: 29 January 2018 DOI: 10.1002/jcb.26754 RESEARCH ARTICLE Simultaneous downregulation of miR-21 and miR-155 through oleuropein for breast cancer prevention and therapy Maryam Abtin 1,2 | Mohammad R. Alivand 2 | Mahmoud S. Khaniani 2 | Milad Bastami 2 | Mohammad Zaeifizadeh 3 | Sima M. Derakhshan 1,2 1 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran 2 Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran 3 Department of Genetic, Ardabil Branch Islamic Azad University, Ardabil, Iran Correspondence Sima M. Derakhshan, Department of Medical Genetics, School of Medicine, Tabriz, University of Medical Sciences, Tabriz, Iran. Email: mderakhshan2002@gmail.com Funding information Immunology research center, Tabriz university of medical science, Tabriz, Iran IR.TBZMED.REC.1395.131347 Abstract Breast cancer (BC) is the leading cause of cancer mortality in women worldwide. It recently was proven that miRNAs play a critical role in BC development. The use of natural agents for control of cancer by modulating miRNAs is promising. Oleuropein is a natural polyphenolic agent with anti-neoplastic properties and is well tolerated by humans. This study was undertaken to determine the therapeutic effects of oleuropein through modulation of master oncomiRs (miR-21 and miR-155) in BC cells. The present study provides the first link between miRNA and oleuropein as a mechanism in BC. MCF-7 cells were tested with and without oleuropein and the cell viability, apoptosis, and migration were examined. The effect of oleuropein on miR-21 and miR-155 expression was assessed through qRT-PCR. It was found that oleuropein induced apoptosis and retarded cell migration and invasion in a dose-dependent manner in the human MCF7 BC cell line. It was observed that oleuropein significantly decreased expression of both miR-21 and miR-155 over time in a dose-dependent manner. These results demonstrate that oleuropein is a potential therapeutic and preventive agent for BC. Oleuropein exhibits an anti-cancer effect by modulation of tumor suppressor gene expression, which is targeted by oncomiRs. KEYWORDS anti-cancer effect, breast cancer, miRNA, miR-21, miR-155, oleuropein 1 | INTRODUCTION Breast cancer (BC) is the most common cancer in women worldwide. Despite widespread research from diagnosis to therapy, it remains the foremost reason of cancer mortality in women. This unwanted effect is the result of its high potential to metastasize, the variety of genetic mutations and the appearance of drug resistance during BC treatment. Recent studies have shown that miRNAs have a key role in BC development, metastasis, drug resistance, and relapse. 1–7 MicroRNAs are small non-coding regulatory RNAs that post-transcriptionally modulate gene expression and play a crucial role in various cell processes. 8,9 Recent studies have identified aberrant expression of miRNAs in human cancers in the oncomiR and tumor suppressor miR (tsmiR) catego- ries. 10,11 Any agent which can alter miRNA ectopic expression is a potential agent for control of cancer. 12 Recent studies have shown that the function of miRNAs in BC are vital and miRNA-targeted therapy is a new aim for BC therapy. 13 A recent advancement in cancer therapeutic method is the use of natural agents or phytochemicals. 14 These tend to be safer J Cell Biochem. 2018;1–15. wileyonlinelibrary.com/journal/jcb © 2018 Wiley Periodicals, Inc. | 1