Bioinformatic Evaluation of microRNAs that Function as potential Regulators of NEK2 and MELK Expression

Objectives: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype in the world and more than 60% of TNBCs are resistant to chemo/radiotherapy. Recently, an analysis of gene expression profiles of patients with TNBC has shown the highly up-regulated NEK2 and MELK genes are associated with drug resistance, rapid relapse and poor outcome in patients. It have been shown these genes are involved in carcinogenesis and cancer progression. MicroRNAs (miRNAs) recruitment represent an attractive strategy for target therapies against TNBC, due to their natural ability to act as antisense regulators of genes. The aim of this study was bioinformatically determining potential miRNAs that may play as a main regulators of NEK2 and MELK expression, also in drug resistance mechanisms of breast cancer. Methods: Bioinformatic analysis was performed using ten different algorithms of miRNA target prediction softwares, such as miRDB, PITA, miRanda and TargetScan based on miRNAs targeting of 3′-untranslated regions of NEK2 and MELK genes. Finally, the candidate miRNAs were analyzed in DIANA and Microcosm softwares. Results: Our results shown that miR-27b-5p with a high score in most softwares, can be considered as a potential regulator of NEK2 and MELK expression. Conclusion: To our knowledge, the role of miR-27b-5p in regulating NEK2 and MELK expression has not been reported in breast carcinogenesis. Therefore, it can contribute to the development of molecular targets as a treatment for TNBC patients; however, the efficacy of this proposed miRNA should be assayed and validated in vitro or in vivo.

کلیدواژه ها:

Triple-negative breast cancer ، NEK2 ، MELK ، Bioinformatic ، miR-27b-5p