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

对天然反义转录本的全转录组分析表明它们在乳腺癌中可能发挥作用

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作者:Stephane Wenric ,Sonia ElGuendi ,Jean-Hubert Caberg ,Warda Bezzaou ,Corinne Fasquelle ,Benoit Charloteaux ,Latifa Karim ,Benoit Hennuy ,Pierre Frères ,Joëlle Collignon ,Meriem Boukerroucha ,Hélène Schroeder ,Fabrice Olivier ,Véronique Jossa ,Guy Jerusalem ,Claire Josse ,Vincent Bours

Abstract

Non-coding RNAs (ncRNA) represent 1/5 of the mammalian transcript number, and 90% of the genome length is transcribed. Many ncRNAs play a role in cancer. Among them, non-coding natural antisense transcripts (ncNAT) are RNA sequences that are complementary and overlapping to those of either protein-coding (PCT) or non-coding transcripts. Several ncNATs were described as regulating protein coding gene expression on the same loci, and they are expected to act more frequently in cis compared to other ncRNAs that commonly function in trans. In this work, 22 breast cancers expressing estrogen receptors and their paired adjacent non-malignant tissues were analyzed by strand-specific RNA sequencing. To highlight ncNATs potentially playing a role in protein coding gene regulations that occur in breast cancer, three different data analysis methods were used: differential expression analysis of ncNATs between tumor and non-malignant tissues, differential correlation analysis of paired ncNAT/PCT between tumor and non-malignant tissues, and ncNAT/PCT read count ratio variation between tumor and non-malignant tissues. Each of these methods yielded lists of ncNAT/PCT pairs that were enriched in survival-associated genes. This work highlights ncNAT lists that display potential to affect the expression of protein-coding genes involved in breast cancer pathology.

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