Identification of a novel circRNA, hsa_circ_0065898, that regulates tumor growth in cervical squamous cell carcinoma

Abstract

Background: Circular RNAs (circRNAs) have been reported to play an important role in regulating tumor pathogenesis and progression. The molecular mechanism of circRNAs in cervical squamous cell carcinoma (CSCC) remains poorly understood. We aimed to identify the circRNAs differentially expressed, and to investigate the role of a novel circRNA, hsa_circ_0065898, in regulating proliferation, migration, and invasion in CSCC.Methods: The online Kaplan-Meier Plotter was used to analyze the relationship between miRNA expression and overall survival. Bioinformatics tools, such as R, Cytoscape, and Perl, were used to analyze the Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein-protein interaction (PPI) network, and regulatory network. The expression level of hsa_circ_0065898 in CSCC cell lines was evaluated using quantitative polymerase chain reaction in vitro. The cell counting kit-8 (CCK-8) and transwell assays were used to assess cell proliferation, migration, and invasion. Results: circRNA expression data (GSE102686) was downloaded from the Gene Expression Omnibus database, and this included data from 5 CSCC patients and 5 normal tissues. Thirteen differentially expressed circRNAs were identified, which included 9 upregulated circRNAs and 4 downregulated circRNAs. GO enrichment analysis showed that the target genes of miRNAs associated with hsa_circ_0065898 were enriched in ubiquitin-protein transferase activity, ubiquitin-like protein transferase activity, core promoter sequence-specific DNA binding, mRNA 3′-UTR AU-rich region binding, core promoter binding, AU-rich element binding, ubiquitin-like protein ligase activity, and transcription corepressor activity. KEGG results showed that the Hippo and p53 signaling pathways played significant role in the pathway network. Hsa_circ_0065898 was significantly overexpressed in the CSCC cell lines. Hsa_circ_0065898 facilitated cell proliferation, migration, and invasion in CSCC.Conclusions: This study identified differentially expressed circRNAs and constructed the regulatory network of hsa_circ_0065898 targeting microRNAs and mRNAs. We demonstrated that hsa_circ_0065898 promoted CSCC cell proliferation, migration, and invasion. Hence, hsa_circ_0065898 might be useful as a biomarker for CSCC diagnosis and targeted therapy.