Abstract
IntroductionLung cancer continues to be a significant health burden in the United States. Lung cancer in never smokers is considered as a different disease and underlying mechanism of spontaneous lung cancer susceptibility is still poorly known. Meanwhile, the roles of long non-coding RNAs (lncRNAs), which have multiple functions in biological processes, have seldom been studied in spontaneous lung cancer susceptibility.MethodsIn this study, microarray analyses of normal lung tissues were performed in 23 different mouse strains. LncRNA profile was analyzed by re-annotating exon array for lncRNAs detection. LncRNA/mRNA co-expression networks were constructed and the association between significant lncRNA module and significant mRNA modules was calculated. Finally, Genome-wide association (GWA) results were used to further highlight the key mRNAs and lncRNAs associated with spontaneous lung cancer susceptibility.ResultsFour mRNA modules were significantly associated with spontaneous lung cancer susceptibility. Genes in these modules were enriched in “blood coagulation” and “immune system process”. Only one lncRNA module was significantly associated with spontaneous lung cancer susceptibility. Many lncRNAs in this module were co-expressed with mRNAs in the second most significant mRNA module. This co-expression network contained 113 interactions between 30 lncRNAs and 40 mRNAs. After GWA filtration, two mRNAs (Myo7a and Zfp874a) and two lncRNAs (n290048 and n271850) were highlighted as the candidates responsible for genetic susceptibility to lung cancer.ConclusionsWe firstly used integrative system genetic analysis to report the mRNA-lncRNA network associated with spontaneous lung cancer susceptibility and identified potential targets for lung cancer prevention.
Highlights
Lung cancer continues to be a significant health burden in the United States
We firstly used integrative system genetic analysis to report the mRNA-long non-coding RNAs (lncRNAs) network associated with spontaneous lung cancer susceptibility and identified potential targets for lung cancer prevention
From the co-expression analysis, we aimed to generate potential mRNA-lncRNA network associated with spontaneous lung cancer susceptibility
Summary
Lung cancer continues to be a significant health burden in the United States. Lung cancer in never smokers is considered as a different disease and underlying mechanism of spontaneous lung cancer susceptibility is still poorly known. Some research groups, including our lab, used inbred mouse model to investigate the mechanism of lung cancers occurring without apparent environmental stimulus (i.e., spontaneous) [4,5,6]. In these studies, using genome-wide association (GWA) analyses and expression quantitative trait loci (eQTLs) analyses, several key genes or loci were identified to be related to spontaneous lung cancer susceptibility. Since the complexity of spontaneous lung cancer pathogenesis, integrated system genetic approaches are needed to investigate the transcriptome data and further increase the probability of identifying key genes and complex cellular networks
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