Balkan Journal of Medical Genetics

MicroRNAs IN BREAST CANCER —OUR INITIAL RESULTS
Popovska-Jankovic K1, Noveski P1, Chakalova L1, Petrusevska G2, Kubelka K3, Plaseska-Karanfilska D1
*Corresponding Author: Professor Dr. Dijana Plaseska-Karanfilska, Research Centre for Genetic Engineering and Biotechnology “Georgi D. Efremov,” Macedonian Academy of Sciences and Arts, Krste Misirkov 2, Skopje 1000, Republic of Macedonia; Tel: +389(0)2 3235410; Fax: +389 (0)2 3115434; E-mail: dijana@manu.edu.mk
page: 87

INTRODUCTION

MicroRNAs (miRNAs) are small [~21-nucleotide (nt)] non coding RNAs (ncRNAs) that mediate posttranscriptional gene regulation by pairing with the 3’ untranslated region (3’UTR) of messenger RNAs (mRNAs), acting as translational repressors, and regulating gene expression posttranscriptionally. After the discovery of the first mi-RNA in the roundworm Caenorhabditis elegans, these short regulatory RNAs have been found to be an abundant class of RNAs in plants, animals and DNA viruses. About 3.0% of human genes encode for miRNAs, and up to 30.0% of human protein coding genes may be regulated by miRNAs [1]. Currently more than 2000 unique human mature microRNAs are known [2]. MicroRNAs play a key role in diverse biological processes including development, cell proliferation, differentiation and apoptosis [1]. Thus, potentially all cellular pathways may be governed by miRNAs, which may contribute to the fine tuning of gene expression on a global level. The importance of miRNAs in gene regulation will be better appreciated when their function or deregulation, or that of the cellular machinery mediating their biosynthesis and function, will be identified among the underlying causes of several genetic disorders. Indeed, it is easy to conceive that protein over expression resulting from defective miRNA-based mRNA regulation may compromise normal cell function and cause genetic diseases [3]. Accordingly, altered miRNA expression is likely to contribute to human disease, including cancer [1]. In cancer, miRNAs function as regulatory molecules, acting as oncogenes or tumor suppressors [4]. Amplification or over expression of miRNAs can down regulate tumor suppressors or other genes involved in cell differentiation, thereby contributing to tumor formation by stimulating proliferation, angiogenesis and invasion, i.e., they act as oncogenes. Similarly, miRNAs can down regulate different proteins with oncogenic activity, i.e., they act as tumor suppressors [5,6]. Several miRNA are associated with breast cancer. It has been shown that there are differences not just between normal and breast cancer tissue, but also between different breast cancer subtypes [7-12]. Several methods for global miRNA profiling are currently in common use. These include quantitative real time-polymerase chain reaction (ReTi-PCR) (qPCR) involving stem-loop reverse transcriptase (RT) primers combined with TaqMan® PCR (Life Technologies, Carlsbad, CA, USA) analysis, qPCR with locked nucleic acid primers (Exiqon, Vedback, Denmark), qPCR using poly(A) tailing (Qiagen, Hilden, Germany; Stratagene, La Jolla, CA, USA), high-throughput sequencing of small RNA libraries and microarray analysis. We have recently initiated a study of microRNAs in breast cancer tissues with a main aim to search for breast cancer diagnostic and prognostic markers.

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