Categorizing the Small RNA Transcriptome in the Intra Thoracic Airways of Former Smokers

Abstract

Smoking is the leading cause of preventable disease and death worldwide. Independent studies on extra thoracic airways elucidated transcriptomic changes associated with diseases on tobacco exposure. Smoking-cessation is the best remedy to reduce the risk of developing diseases. Despite the fact, some former smokers are still at a high risk of developing diseases. The query why some former smokers develop disease decades after they have quit smoking is yet to be answered. We have employed Deep RNA sequencing (Illumina HiSeq 2000 platform) to investigate small RNA transcriptome of bronchial epithelial samples of 79 current and 138 former smokers. Former smokers were categorized according to tobacco abstinence and cumulative tobacco exposure. Linear regression models were used in conjunction with SVA to determine differentially expressed miRNAs between current and former smokers and their difference in kinetics according to time since quit in former smokers. Similar statistical analysis of mRNA microarray data of matched samples helped in extraction of putative targets of smoking related miRNAs. Linear models identified 66 differentially expressed miRNAs and their corresponding 184 targets between current and former smokers at FDR<0.05. Biological interpretation of miRNAs and their putative targets has provided an insight of smoking induced disruption of regulatory mechanisms and their behavior with smoking cessation. We conclude that former smokers with prolonged abstinence and low cumulative tobacco have non-persistent transcriptomic changes. The findings of this study will pave the path to postulate pervasiveness of disease within former smokers.