Function of miRNAs in tumor cell proliferation

MicroRNAs (miR) are a class of multifunctional, small, non-coding, singled-stranded molecules that regulate the stability or translational efficiency of targeted messenger RNAs. According to the miRBase Sequence Database (http://www.mirbase.org/index.shtml), more than 1,000 miR sequences have been identified from the tissues or cells of human origin. miRNAs are transcribed from the genome mostly by RNA polymerase II into primary miRNAs (called pri-miRNA) which are usually around 1 kb in length. pri-miRNAs Pri-miRNA are further processed in the nucleus by a ribonucleases complex composed of Drosha Drosha and DGCR8 DGCR8 into precursor miRNAs (called pre-miRNAs) which are around 70-90 nucleotides in length with imperfectly complementary stem-loop-stem structures. The pre-miRNA is then transported by exportin-5, a pre-miRNA-specific export carrier, to the cytoplasm where the pre-miRNA is cleaved by another ribonuclease, Dicer, into a double-stranded miRNA which consists of a mature miRNA sequence of about 17-25 nucleotides long and a miRNA∗fragment (derived from the opposite strand to the mature miRNA strand). The mature miRNA is assembled into a ribonucleoprotein complex known as RNA-induced silencing complex (RISC) that includes Argonaute Argonaute protein [1]. The miR-RISC complex could lead to base-pairing interactions between a miRNA and the binding site of its target mRNAs within the 3′ untranslated region (3′UTR). The interaction could lead to endonucleotic cleavage of the target mRNA or interference with its ability to be translated depending on the base-pairing complementarity between the miRNA and the target mRNA [2, 3].