Identification of POLQ as a key gene in cervical cancer progression using integrated bioinformatics analysis and experimental validation.

Abstract

As the most common gynecologic malignancy worldwide, cervical cancer (CC) is a serious hazard to health. Therefore, the present study aimed to identify the key genes in CC progression using integrated bioinformatics analysis and experimental validation. The mRNA microarray GSE63514 and microRNA (miRNA) microarray GSE86100 were obtained from the Gene Expression Omnibus database, and the differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) in the progression of CC were identified. Thereafter, GO and KEGG functional enrichment analysis, protein‑protein interaction (PPI) network and significant subnetworks construction, and miRNA‑target regulatory network construction were performed. Based on the results of integrated bioinformatics analysis, the DEGs structural maintenance of chromosomes 4 (SMC4), ATPase family, AAA domain‑containing 2 (ATAD2) and DNA polymerase θ (POLQ) were identified as hub genes in the PPI network and were involved in the first significant subnetwork. In addition, these DEGs were predicted to be regulated by miR‑106B, miR‑17‑5P, miR‑20A and miR‑20B, which were identified as DEMs. Of note, SMC4 and ATAD2 are tumor‑promotors in CC. In the present study, small interfering (si)RNAs were used to knock down POLQ expression. Cell Counting Kit‑8, Transwell, cell cycle and apoptosis analyses revealed that the downregulation of POLQ restrained cell proliferation, migration and invasion, and promoted apoptosis and the arrest of the cell cycle in the G2 phase. In conclusion, POLQ, which may have a close interaction with SMC4 and ATAD2, may serve a vital role in the progression of CC.