Abstract
RNA editing in microRNAs has been recently proposed as a novel biomarker in cancer. Here, we 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, we detected deregulated microRNA editing events between NSCLC tumor and normal tissues. Interestingly, and for the first time, we 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.
Highlights
RNA editing is a widespread molecular phenomenon in metazoa[1] that involves base substitution of nucleotides within RNA2
The miRNA editing phenomenon has been studied by exclusively considering the editing level, which is based on the expression of the miRNA itself (Editing Level = ED miRNA/(ED miRNA + WT miRNA)
We apply a new concept for miRNA editing measurement, which considers the editing level and the expression of ED and WT miRNAs assessed via reads per million reads mapped to miRNAs (RPM)
Summary
RNA editing is a widespread molecular phenomenon in metazoa[1] that involves base substitution of nucleotides within RNA2. A-to-I RNA editing events, defined as “canonical editing sites”, occur in coding mRNA sequences and may alter the amino acid sequence of the encoded protein, influencing both function and regulation[2,6]. Using the editing level and miRNA expression, we identified deregulation of ED miRNAs between tumor and normal samples in both LUAD and LUSC, respectively. This latter parameter proved to be more efficient in distinguishing normal and tumor tissues in both types of lung cancer. One of these circulating ED miRNAs, miR-411–5p edited in position 5, was differentially expressed between NSCLC and normal tissue samples
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