A ceRNA network of BBOX1-AS1-hsa-miR-125b-5p/hsa-miR-125a-5p-CDKN2A shows prognostic value in cervical cancer

Cervical cancer (CC) ranks fourth most diagnosed cancer and cancer mortality in women. Long non-coding RNAs (lncRNAs) take important roles in CC development. This study aimed to identify more and novel competing endogenous RNA (ceRNA) mechanisms of lncRNAs in CC.

The miRNA expression dataset GSE20592 and lncRNA/mRNA expression dataset GSE63514 were downloaded from Gene Expression Omnibus. The differentially expressed genes (DEGs), differentially expressed lncRNAs (DElncRNAs), and differentially expressed miRNAs (DEmiRNAs) between CC tumor and normal samples were identified with the criteria of adj.P.Value < 0.05 (Benjamini & Hochberg) and |log₂(fold change)|>2. Functional enrichment analysis was performed for DEGs. The interaction pairs among lncRNAs, miRNAs and mRNAs were predicted and the ceRNA network was then constructed. Survival analysis was performed based on the TCGA dataset.

Totally, 42 DEmiRNAs, 25 DElncRNAs, and 518 DEGs were identified in CC tumor samples versus normal tissues. The DEGs were associated with 'GO:0006260: DNA replication', 'GO:0051301: cell division', and 'hsa01100:Metabolic pathways'. The ceRNA network consisted of 878 lncRNA-miRNA-mRNA pairs. Of the miRNAs, lncRNAs, and genes with the top 10 interaction degrees in the ceRNA network, the upregulated cyclin dependent kinase inhibitor 2A gene (CDKN2A) was targeted by the downregulated DEmiRNAs including hsa-miR-125b-5p and hsa-miR-125a-5p, which were targeted by the upregulated DElncRNA BBOX1-AS1. The high expression level of CDKN2A contributed to the poor overall survival of patients with CC.

The BBOX1-AS1-hsa-miR-125b-5p/hsa-miR-125a-5p-CDKN2A ceRNA network is of great value in CC development.