In-Silico Identification and Analysis of miRNAs and mRNAs in Lung Adenocarcinoma

Abstract

Lung cancer is considered as one of the dominant causes of cancer deaths worldwide. Lung cancer is divided into small cell lung cancer, adenocarcinoma, large cell carcinoma and squamous cell carcinoma. Out of these, lung adenocarcinoma is responsible for 50% of cases. Smoking is one of the major risk factors contributing to this malignancy but patients without smoking history are also affected by lung adenocarcinoma. Increasing mortality rate can be managed by getting insights into the molecular biology of smokers and non-smokers in lung adenocarcinoma that can facilitate in early diagnosis along with discovery of novel therapeutics. MicroRNAs play important roles in different physiological activities by regulating mRNAs. The major objective of this research is to find any novel associations between miRNAs and their target mRNAs in lung adenocarcinoma compared to normal ones. Differences in genetic profiles of smokers and non-smokers in lung adenocarcinoma are also explored. Differential expression analysis is performed on miRNAs and mRNAs using microarray analysis and RNA-Seq analysis respectively. Gene co-expression network analysis is also performed to get modules significantly correlated with lung adenocarcinoma. Results have shown that miRNA/mRNA pairs were found dysregulated in lung adenocarcinoma. These pairs include dysregulation of miR-671-5p/PRKAA1, miR- 501-3p/TFDP2, miR-940/TFDP2, miR-142-5p/SRP9, miR-142-5p/ACAT1, miR-542- 3p/ACAT1, miR-542-3p/SRP9, miR-501-5p/TFRC and miR-498/TFRC significantly dysregulated in non-smokers with lung adenocarcinoma. ASH1L is regulated by 5 miRNAs (miR-107, miR-503, miR-498, miR-429 and miR-557) and this gene was also found dysregulated in non-smokers. In smokers two miRNA/mRNA pairs (miR- 133b/PRKCZ and miR-557/STEAP3) have shown significant disruptions in their expressions. These miRNAs and their targets are also regulators of important biological pathways including cell cycle, signaling pathways and metabolic pathways revealing them as potential biomarkers and therapeutic targets in lung adenocarcinoma.