Integrated analysis of key microRNAs /TFs /mRNAs/ in HPV-positive cervical cancer based on microRNA sequencing and bioinformatics analysis.

Background: Cervical squamous cell carcinoma (CESC) is one of the most common malignancies associated with mortality in females. Its onset and prognosis are primarily concerned with persistent infection with high-risk types of human papillomavirus (HPV). However, the molecular mechanisms of HPV-positive CESC remain unclear.

Methods: In this study, we conducted a high-throughput sequencing to identify differentially expressed miRNAs (DEMs). Besides, three series were selected from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). Then the miRNA-TF-gene regulatory network was constructed using bioinformatic methods. Genes in the network were performed functional enrichment analysis and protein-protein interaction (PPI) network analysis. Ultimately, the expression levels of six key miRNAs, TFs, and mRNAs were validated by 20 HPV-positive CESC tissues and 15 normal cervical samples.

Results: A total of 52 DEMs and 300 DEGs differed between the HPV-positive CESC and normal cervical samples. Then the miRNA-TF-gene regulatory network was constructed consisting of 22 miRNAs, 6 TFs, and 76 corresponding genes, among which miR-149-5p, miRNA-1248 and E2F4 acted as key regulators. PPI network analysis showed that ten genes including TOP2A, AURKA, CHEK1, KIF11, MCM4, MKI67, DTL, FOXM1, SMC4, and FBXO5 were recognized as hub genes with the highest connectivity degrees. Besides, five key molecules miRNA-149-5p, E2F4, KIF11, DTL, and SMC4 were suggested to play crucial roles in the development of HPV-positive CESC.

Conclusion: These results present a unique insight into the pathological mechanisms of HPV-positive CESC and possibly provides potential therapeutic targets.