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.
