Reducing false positive prediction of miRNA target genes with RNA sequencing: Hype or hope

The microRNAs (miRNAs) regulate many biological processes and their altered expression is reported in many diseases including cancer [1-5], diabetes [6-8], and liver fibrosis [9-11]. They are never translated but manipulate gene expression by base-pairing with the 3' untranslated region (UTR) of their target mRNAs. Firstly, they were discovered as a short RNA produced by the lin-4 gene in Caenorhabditis elegans which represses the lin-14 mRNA. Initially, it was thought that they are unique only to nematodes but now it is well demonstrated that they are abundant in the diverse animal kingdom. It is also well established that they are involved in every cellular process including cell differentiation, proliferation, apoptosis, metastasis, and chemoresistance. More than 60% of protein-coding genes in the human harbor’s miRNA target site [12]. In cancer, they can be oncomirs (oncogenes), tumor suppressors, prognostic markers, or therapeutic target. Since the expression pattern of miRNAs are highly specific, and functionally they regulate at the epigenetic level in genome, they are attractive biomarkers in medical research. These relatively new class of gene regulators has opened a new direction for drug discovery. Interest in miRNA-based therapy is now growing rapidly and literature is getting enriched with novel miRNAs and their