Editing sites detected in the microRNA cargo of circulating exosomes

RNA editing in microRNAs has been recently proposed as a novel biomarker in cancer. Here, researchers at the Ohio State University investigated RNA editing by leveraging small-RNA sequencing data from 87 NSCLC (Non-Small Cell Lung Cancer) samples paired with normal lung tissues from The Cancer Genome Atlas (TCGA) combined with 26 plasma-derived exosome samples from an independent cohort. Using both the editing levels and microRNA editing expression, they detected deregulated microRNA editing events between NSCLC tumor and normal tissues. Interestingly, and for the first time, the researchers also detected editing sites in the microRNA cargo of circulating exosomes, providing the potential to non-invasively discriminate between normal and tumor samples. Of note, miR-411-5p edited in position 5 was significantly dysregulated in tissues as well as in exosomes of NSCLC patients, suggesting a potential targetome shift relevant to lung cancer biology.

A-to-I miRNA editing hotspots in plasma-derived exosome NSCLC samples

(a) Statistics for miRNA editing hotsposts and WT counterparts in normal and tumor (early/late stage) plasma-derived NSCLC samples. Hotsposts occurring within MSRs are in light blue, while those outside the MSR are in light orange. Pvalues were calculated with the following methods respectively: Mann-Withney paired test for editing level; paired t-test for ED\WT miRNA expression; Pearson correlation test between WT\ED miRNA expressions. In significant pvalues (P < 0.05) are in green. (b) Diagram of stem-loop nucleotide sequence for miR-411. The -5p mature sequence is highlighted in blue, while in green is the -3p. Seed sequence nucleotides are indicated in red, with the editing site highlighted in yellow. (c) Box-plot diagrams of expression values (RPM) and editing levels for both edited miRNAs detected across normal, early and late stage NSCLC samples.