IDENTIFICATION OF POLQ AS A KEY GENE IN CERVICAL CANCER PROGRESSION USING INTEGRATED BIOINFORMATICS ANALYSIS AND EXPERIMENTAL VALIDATION

Problem statement. As the most common gynecologic malignancy worldwide, cervical cancer (CC) is a serious hazard to women’s health. Therefore, the present study aimed to identify the key genes in CC progression using integrated bioinformatics analysis and experimental validation.

Methods. The mRNA microarray and microRNA (miRNA) microarray 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. GO and KEGG functional enrichment analysis, protein-protein interaction (PPI) network and significant subnetworks construction, and miRNA-target regulatory network construction were performed. Then, experiments in vitro were performed to validate the roles of the key gene in CC progression identified based on the results of integrated bioinformatics analysis.

Results. Based on the mRNA dataset, GSE63514, a total of 1,318 DEGs were screened upon comparison of the CIN sample data with those of normal cervical epithelium samples, and 1,575 DEGs were screened between CC and cervical intraepithelial neoplasia tissues. Furthermore, based on the miRNA dataset, GSE86100, 166 DEMs were screened. According to the results of 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 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. Therefore, it was hypothesized that the three DEGs (SMC4, ATAD2 and POLQ) may interact closely with each other in CC progression. Of note, SMC4 and ATAD2 are proved to be tumor-promotors in CC by previous studies. And in the present study, the roles of POLQ in CC progression were validated by cells transfection of small interfering (si)RNAs and Cell Counting Kit-8, Transwell, cell cycle and apoptosis analyses, and the results 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.

Conclusion. POLQ, which have a close interaction with SMC4 and ATAD2, may serve a vital role in the progression of CC.