MicroRNA-Based Diagnosis and Therapy

Abstract

MicroRNAs (miRNAs) are a group of endogenous non-coding RNAs that regulate gene expression. Alteration in miRNA expression results in changes in the profile of genes involving a range of biological processes, contributing to numerous human disorders. With high stability in human fluids, miRNAs in the circulation are considered as promising biomarkers for diagnosis, as well as prognosis of disease. In addition, the translation of miRNA-based therapy from a research setting to clinical application has huge potential. The aim of the current review is to: (i) discuss how miRNAs traffic intracellularly and extracellularly; (ii) emphasize the role of circulating miRNAs as attractive potential biomarkers for diagnosis and prognosis; (iii) describe how circulating microRNA can be measured, emphasizing technical problems that may influence their relative levels; (iv) highlight some of the circulating miRNA panels available for clinical use; (v) discuss how miRNAs could be utilized as novel therapeutics, and finally (v) update those miRNA-based therapeutics clinical trials that could potentially lead to a breakthrough in the treatment of different human pathologies.

Keywords: circulating microRNA; clinical application; miRNA-based diagnosis; miRNA-based therapy; prognosis.

Figure 1

miRNA biogenesis and extracellular export. MicroRNAs are first transcribed by RNA polymerase II as primary (pri-miRNA) transcripts in the nucleus. The pri-miRNA are cut by the Drosha/DGCR8 complex to pre-miRNA precursors that transport into the cytoplasm by Exportin. In the cytoplasm, pre-miRNAs are further cut by Dicer in a complex with TRB, resulting the miRNA duplex. The mature miRNA incorporates with an AGO protein forming miRISC complex which will interact with the target mRNA and suppress its expression. Three ways that miRNAs can be undergone into circulation: mediated by extracellular vesicles (exosomes) (green arrows) or other RNA-binding proteins such as Ago (red arrows) or NPM1 (blue arrows). HDL, high-density lipoprotein. NPM1, nucleophosmin 1. POL III, RNA polymerase. TRB, T cell receptor beta.

Figure 2

Summary of modulated circulating microRNAs in several prominent cancer types including breast cancer, lung cancer, prostate cancer, colorectal cancer, liver cancer. Circulating miRNAs were from serum (black), plasma (white), and blood (green) of both cancers diagnosed and control counterparts with their levels (either increase or decrease) shown.

Figure 3

miRNA-based diagnostic tools available in clinic.

Figure 4

Biological molecular methods for microRNA detection and quantification. (A) Northern blot; (B) poly (A) real-time reverse transcriptase PCR; (C) stem–loop real-time reverse transcriptase PCR; (D) digital PCR.

Figure 5

(A) Chemical modifications of oligonucleotides; (B) miRNA replacement therapy using miRNA mimics, miRNA mimic triple strand; miRNA inhibition therapy using miRNA antagomirs, miRNA inhibitors, and miRNA sponges; (C) Current miRNA-based therapy.