An Integrative Transcriptomic Analysis Reveals EGFR-19 Exon Mutation Regulated miRNA, circRNA, mRNA and lncRNA Networks in Lung Carcinoma

Abstract

Background: Competing endogenous RNA (ceRNA) appear to be an important post-transcriptional manner that regulates gene expression through a miRNA-mediated mechanism. Mutations in exon 19 of EGFR were frequently observed in lung cancers gene, which were associated with EGFR activity and the EGFR-targeted therapies. In this study, we explored the transcriptome regulated by mutation in exon 19 of EGFR gene by using a network modeling strategy. The identification of RNA was related to the mutation of exon EGFR19 and can be used for clinical prognosis and treatment. Methods and Findings: We applied transcriptome sequencing to detect the deletion process of EGFR 19 exon E746-A750 fragment. First, the differentially expressed genes were screened by comparing EGFR19 D (exon 19 E746-A750 deletion) and EGFR19 N (exon 19 wild-type) tissues. The mRNA and non-coding RNA expression profiles in these tissues with different mutation allele in EGFR exon19 were distinct. Then, bioinformatic analyses were used to predict the gene targets and explain their potential roles in tumorigenesis and progression of lung cancer. Finally, an intersection analysis of microarray data showed that 33 miRNAs, 80 lncRNAs and 15 circRNAs were involved in the EGFR-19 exon E746-A750 fragment deletion process, Meanwhile, the significant pathways and biological functions potentially regulated by the deregulated 128 non-coding genes were enriched. Interpretation: Our work provides an important theoretical, experimental and clinical foundation for further research on more effective targets for the diagnosis, therapy and prognosis of lung cancer. Funding Statement: This study was supported by the grants of national natural science fund (81701511), grants of Wuxi Young Medical Talents Program (QNRC016, QNRC017). Declaration of Interests: The authors declare no competing interests with relevance to this study. Ethics Approval Statement: The ethics committee sanctioned the collection of the specimens, and the patients gave written informed consent.