Locked nucleic acid as a novel technology for high affinity and accurate targeting of miRNAs in breast cancer diagnosis

Background and aims: MicroRNAs (miRNAs) are a novel class of short endogenous non-coding RNAs which act as post-transcriptional modulators of gene expression. Perturbed miRNA expression patterns have been observed in many human cancers, including breast cancer. Hence aberrant miRNA expression might be of potential use asdiagnostic and prognostic biomarker of these cancers. However, because of small size of miRNAs, the detection of mature miRNAs has been technically challenging. Locked nucleic acid (LNA) is a nucleic acid analogue containing one or more LNA nucleotide monomers with a bicyclic furanose unit locked in an RNA mimicking sugar conformation.This conformational restriction results in unprecedented hybridization affinity towards complementary single stranded RNA, and thus makes LNA uniquely suited for mimicking RNA structures and sequence specific targeting of RNA as antisense molecules in vitro or in vivo. In this article, at first we briefly describe the basic physiochemical properties of LNA. The central part of the review focuses on the mechanism underlying detection and analysis of microRNAs by LNA-modified oligonucleotide probes. Methods: By using miRNA databases and reviewing literatures, we have concentrated useful information in order to introduce the use of LNA technology for efficiently targeting of miRNAs in breast cancer researches. Results and conclusion: The remarkable hybridization properties of LNA, with respect to both affinity and specificity,position LNA as an enabling molecule for molecular biology research and RNA targeting. Use of LNA probes to target miRNAs increases thermal stability and hybridization specificity. Therefore, more accurate gene quantitation and allelic discrimination would be resulted.

Keywords:

miRNA , breast cancer , cancer diagnosis , LNA technology