Reconstruction and analysis of circRNA-miRNA-mRNA network in the pathology of lung cancer

Summary Background: The presented study aimed to gain insights into the pathogenesis of lung cancer (LC) and provide novel bio markers for LC by building a regulatory circular (circ)RNA-micro (mi)RNA-mRNA network . Materials and methods: High-throughput sequencing data of circRNAs, miRNAs and mRNAs related to LC originated from GEO (Gene Expression Omnibus) database, and the differential expressions of circRNAs, miRNAs and mRNAs were screened with R language Limma . The circRNA-miRNA and miRNA-mRNA pairs were used to build the ceRNA network . The functions of differential expression circRNAs were elucidated by performing the functional enrichment analysis on GO and KEGG . Furthermore, the selected LC prognostic genes were verified by tissue chips and immunohistochemistry (IHC) . Results: On the whole, 20 downregulated circRNAs, 55 upregulated miRNAs and 243 downregulated mRNAs were identified in LC . Lastly, a circRNA-miRNA-mRNA ceRNA network was built, which was composed of 2 circRNAs, 2 miRNAs, and 2 mRNAs . As indicated from the analysis based on public databases and IHC, the differential genes (i . e . , FXYD1 and SEMA5A) in this network acted as LC prognostic factors . As confirmed by performing IHC and survival analyses, FXYD1 and SEMA5A expressions in LC were downregulated, and their expressions displayed a relationship to the overall survival (OS) of LC cases . Conclusions: This study presents novel insights into the role of circRNAs in the development of LC via the ceRNA mechanism . The identified FXYD1 and SEMA5A gene could act as novel and vital LC prognostic indicators .