Abstract
We investigated the transcriptional mechanism underlying lung cancer development. RNA sequencing analysis was performed on blood samples from lung cancer cases and healthy controls. Differentially expressed microRNAs (miRNAs), circular RNAs (circRNAs), mRNAs (genes), and long non-coding RNAs (lncRNA) were identified, followed by pathway enrichment analysis. Based on miRNA target interactions, a competing endogenous network was established and significant nodes were screened. Differentially expressed transcriptional factors were retrieved from the TRRUST database and the transcriptional factor regulatory network was constructed. The expression of 59 miRNAs, 18,306 genes,232 lncRNAs, and 292 circRNAs were greatly altered in patients with lung cancer. miRNAs were closely associated with cancer-related pathways, such as pathways in cancer, colorectal cancer, and transcriptional misregulation in cancer. Two novel pathways, olfactory transduction and neuroactive ligand-receptor interactions, were significantly enriched by differentially expressed genes. The competing endogenous RNA network revealed 5 hub miRNAs. Hsa-miR-582-3p and hsa-miR-582-5p were greatly enriched in the Wnt signaling pathway. Hsa-miR-665 was closely related with the MAPK signaling pathway. Hsa-miR-582-3p and hsa-miR-582-5p were also present in the TF regulatory network. Transcriptional factors of WT1 (wilms tumor 1) and ETV1 (ETS variant 1) were regulated by hsa-miR-657 and hsa-miR-582-5p, respectively, and controlled androgen receptor gene expression. miR-582-5p, miRNA-582-3p, and miR-657 may play critical regulatory roles in lung tumor development. Our work may explore new mechanism of lung cancer and aid the development of novel therapy.
Highlights
Lung cancer has a high incidence and mortality and threatens public health worldwide
The expression of 59 miRNAs, 18,306 genes,232 long non-coding RNAs (lncRNA), and 292 circRNAs were greatly altered in patients with lung cancer. miRNAs were closely associated with cancer-related pathways, such as pathways in cancer, colorectal cancer, and transcriptional misregulation in cancer
Cross-talk between competing endogenous RNA (ceRNA) based on shared miRNAs plays key roles in the physiology and development of various cancers [11]
Summary
Lung cancer has a high incidence and mortality and threatens public health worldwide. Recent data have suggested that lung cancer is the leading cause of cancerrelated deaths [1]. 1.82 million people are estimated to be affected by lung cancer, resulting in 1.67 million cancer deaths in 2012 worldwide [1]. Lung cancer is caused by the combined effects of genetic and environmental factors. Despite progress in understanding the pathogenesis of lung cancer, the prognosis of lung cancer remains poor with a 5-year survival of less than. With the development of molecular biology techniques, novel therapeutic targets and prognostic biomarkers for lung carcinogenesis have been discovered
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