MicroRNAs (miRNAs) constitute a large family of small, approximately 20-22 nucleotide non-coding RNAs that regulate the expression of target genes, mainly at the post-transcriptional level. Multiple studies report that miRNAs are involved in homeostatic maintenance and that aberrant expression of miRNAs is often observed in various types of diseases, including cancer. In cancer biology, miRNAs exert functional roles in tumor initiation, drug resistance, and metastasis. MiRNAs are also secreted through small vesicles called exosomes, which are endosome-derived vesicles derived from various cell types including immune and tumor cells. In addition to cellular miRNAs (ce-miRNAs), secreted miRNAs (se-miRNAs) play important roles in cancer development and metastasis. Therefore, se-miRNAs in body fluids have been investigated as a promising biomarkers and therapeutic targets for cancer treatment.
Biogenesis and function of cellular and exosomal microRNA
MiRNAs are transcribed by RNA polymerase II or III as pri-miRNA, and then processed in the nucleus by Drosha-DGCR8 into pre-miRNA. The pre-miRNA is exported to the cytoplasm by exportin-5 and further cleaved by a complex composed of Dicer and TRBP. The functional strand of mature miRNA is incorporated into the RNA-induced silencing complex (RISC), which contains GW182 and Argonaute protein. As a component of this complex, the mature miRNA regulates gene expression by binding to partially complementary sequences in the 3′UTRs or coding regions of target mRNAs, leading to mRNA degradation or translational repression.