MicroRNAs Regulated Brain Tumor Cell Phenotype and Their Therapeutic Potential

MicroRNAs (miRNAs)are short 18–25 nucleotide small non-coding RNA molecules that function to silence gene expression via sophisticated post-transcriptional regulation[1]. Since their discovery in the early 1990s, these small molecules have been shown to play an important regulatory role in a wide range of biological and pathological processes. Over 30% of human messenger RNAs (mRNAs) are regulated by miRNAs[2]. miRNAs generated by the canonical biogenesis pathway are transcribed as precursor RNAs from intergenic, intronic or polycis‐ tronic genomic loci by RNA polymerase II (Pol II). The primary miRNA (pri-miRNA) transcript forms a stem–loop structure that is recognized and processed by the Drosha and DGCR8 RNase III complex or the spliceosome apparatus in the nucleus. In the non-canonical miRNA pathway, miRNAs are transcribed directly as endogenous short hairpin RNAs (endo-shRNAs) or derive directly through splicing from introns that can refold into hairpins (mirtrons). The trimmed precursor (pre-miRNA) hairpins from both canonical and non-canonical miRNA pathways are then transported by an exportin 5 and RAN-GTP-dependent process to the cytosol, where they are typically further processed by the Dicer and transactivation-response RNA-binding protein (TRBP) RNase III enzyme complex to form the mature double-stranded ~22-nucleotide miRNA. Argonaute proteins (for example, AGO2)