MicroRNA: Biogenesis, Function and Role in Cancer

Abstract

MicroRNAs are small, highly conserved non-coding RNA molecules involved in the regulation of gene expression. MicroRNAs are transcribed by RNA polymerases II and III, generating precursors that undergo a series of cleavage events to form mature microRNA. The conventional biogenesis pathway consists of two cleavage events, one nuclear and one cytoplasmic. However, alternative biogenesis pathways exist that differ in the number of cleavage events and enzymes responsible. How microRNA precursors are sorted to the different pathways is unclear but appears to be determined by the site of origin of the microRNA, its sequence and thermodynamic stability. The regulatory functions of microRNAs are accomplished through the RNA-induced silencing complex (RISC). MicroRNA assembles into RISC, activating the complex to target messenger RNA (mRNA) specified by the microRNA. Various RISC assembly models have been proposed and research continues to explore the mechanism(s) of RISC loading and activation. The degree and nature of the complementarity between the microRNA and target determine the gene silencing mechanism, slicer-dependent mRNA degradation or slicer-independent translation inhibition. Recent evidence indicates that P-bodies are essential for microRNA-mediated gene silencing and that RISC assembly and silencing occurs primarily within P-bodies. The P-body model outlines microRNA sorting and shuttling between specialized P-body compartments that house enzymes required for slicer -dependent and -independent silencing, addressing the reversibility of these silencing mechanisms. Detailed knowledge of the microRNA pathways is essential for understanding their physiological role and the implications associated with dysfunction and dysregulation.

miRNA-34a enhances the sensitivity of gastric cancer cells to treatment with paclitaxel by targeting E2F5

“…An increasing number of studies have suggested that miRNAs are a class of small highly conserved molecules that perform a crucial role in the regulation of multiple cellular events including cellular proliferation, differentiation, development and apoptosis (8,20,21). Dysregulation and dysfunction of miRNAs leads to the initiation and development of cancers, indicating that miRNAs are important molecules that can potentially be used for the diagnosis and treatment of cancers (22).…”

miRNAs as Biomarkers and Therapeutic Targets in Non-Small Cell Lung Cancer: Current Perspectives

“…The standard miRNA biogenesis pathway consists of two cleavage events, one nuclear and one cytoplasmic [21]. After the cleavage, primary miRNAs are processed into active mature miRNAs through a series of biochemical steps, and miRNA expression can be regulated at each step of biogenesis pathway (Fig.…”

miR-17-5p down-regulation contributes to erlotinib resistance in non-small cell lung cancer cells

“…The miRNAs can induce target mRNA degradation and translational repression through its recognition elements pairing to 3 0 -untranslated region (3 0 -UTR) of the target mRNAs [15,16]. Moreover, dysregulation of miRNA also has been observed in cancers including NSCLC [17,18]. Blower et al have studied the effect of miRNAs on chemotherapy and find that the expression patterns of miRNAs is significantly correlated with the potency patterns of 3089 chemical compounds [19].…”