microRNAs Downregulation in Cancer is Associated with Guanine Enrichment in the Terminal Loop Sequences of their Precursors

Background: microRNAs (miRNAs) are small noncoding segments of RNA that negatively regulate gene expression at the post-transcriptional level and fine-tune gene functions. A global repression in miRNA expression is a phenomenon observed in different types of cancer. In this study we aimed to reveal a possible association of miRNAs downregulation in cancer, with the guanine (G) content in the terminal loop (TL) sequences of their precursors. Methods: Lists of most significantly downregulated miRNAs in different tumor types, obtained from previously published microarray experiments, were selected for bioinformatics analysis. The complete precursor, TL, and mature miRNA sequences, were analyzed for evaluation of nucleotide composition and motif enrichment. Results: Herein, we show an association of miRNAs downregulation in cancer, with G enrichment in the TL sequences of their precursors. High G (and GG) content was mostly found in repressed miRNAs of breast, lung and ovary cancers, predominantly in poorly differentiated tumors. The mature sequences of repressed miRNAs had significantly low G content and were enriched with an ACA motif. Conclusion: This study suggests a new link between G enrichment of precursor miRNAs TLs and carcinogenesis, and the possible association of specific sequence motifs with the regulation of their expression.