Identification of potential miRNAs and candidate genes of cervical intraepithelial neoplasia by bioinformatic analysis

Purpose: The objective of this study was to predict potential target genes and key miRNAs for cervical intraepithelial neoplasia (CIN) by bioinformatics analysis. Materials and Methods: The microarray data of GSE51993 were downloaded from Gene Expression Omnibus (GEO) database. Total 30 chips data from two platforms (each platform including eight CIN III samples data and seven normal cervix samples data) were used to identify the feature miRNAs and genes between CIN III and normal samples, respectively. Then the miRNAmRNA regulatory network was constructed using Cytoscape software. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed for all target genes with the Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool. Transcription factors (TFs) and cancer-related genes were analyzed. Results: Total 21 putative target miRNAs and 361 putative target mRNAs were gained. The miRNA-mRNA regulatory network results showed that miR-338- 5p, miR-193a-5p, and miR-216b were top three hub nodes. GO terms significantly enriched were extracellular region (p = 0.004191) and embryonic skeletal system (p = 0.004742). No significantly enriched KEGG pathway term was found in this study. PBX1 (pre-B-cell leukemia transcription factor 1) and LAMC2 (laminin subunit gamma-2) were cancer-promoting genes and also, PBX1 was TF. Conclusions: PBX1 and LAMC2 may be target genes for CIN. MiR-338, and miR-216 may be key miRNAs in CIN development.

Cervical intraepithelial neoplasia; Bioinformatics; miRNA-mRNA regulatory network.

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