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

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) RNAmicro (mi) RNAmRNA network.

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).

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.

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.