Transcriptome wide analysis of natural antisense transcripts shows their potential role in breast cancer.

Non-coding RNAs (ncRNA) represent at least 1/5 of the mammalian transcript amount, and about 90% of the genome length is actively transcribed. Many ncRNAs have been demonstrated to play a role in cancer. Among them, natural antisense transcripts (NAT) are RNA sequences which are complementary and overlapping to those of protein-coding transcripts (PCT). NATs were punctually described as regulating gene expression, and are expected to act more frequently in cis than other ncRNAs that commonly function in trans. In this work, 22 breast cancers expressing estrogen receptors and their paired healthy tissues were analyzed by strand-specific RNA sequencing. To highlight the potential role of NATs in gene regulations occurring in breast cancer, three different gene extraction methods were used: differential expression analysis of NATs between tumor and healthy tissues, differential correlation analysis of paired NAT/PCT between tumor and healthy tissues, and NAT/PCT read count ratio variation between tumor and healthy tissues. Each of these methods yielded lists of NAT/PCT pairs that were demonstrated to be enriched in survival-associated genes on an independent cohort (TCGA). This work allows to highlight NAT lists that display a strong potential to affect the expression of genes involved in the breast cancer pathology.