Dataset Information

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

ABSTRACT:

Background

Circular RNAs (circRNAs) were reported to play an important role in regulating tumor pathogenesis. 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. 13 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, and so on. KEGG 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.

SUBMITTER: Li N

PROVIDER: S-EPMC8797878 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe purpose of this study was to investigate the prognostic signature of necroptosis-related lncRNAs (NRLs) and explore their association with immune-related functions and sensitivity of the therapeutic drug in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC).MethodsUCSC Xena provided lncRNA sequencing and clinical data about CESC, and a necroptosis gene list was obtained from the KEGG database. NRLs were selected by structuring a co-expression network of lncRNAs and necroptosis-related genes. To further screen lncRNAs, we used the univariate Cox regression method, Lasso regression, and multivariate Cox regression. Afterward, an NRL signature was established. We used the xCell algorithm and single-sample gene set enrichment analysis (ssGSEA) to clarify the pertinence between immune infiltration and NRL expressions in CESC patients and explored the relationship between the target lncRNAs and immune-related genes. By leveraging the GDSC database, the therapy-sensitive response of the prognostic signature was forecasted and an experimental validation was performed. We performed GSEA with the aim of recognizing the potential pathway related to the individual prognostic signature.ResultsThe two prognostic NRLs (AC009095.1 and AC005332.4) showed significant diversity and constituted the NRL signature. On the grounds of our signature, risk score was an independent element which was bound up with patient outcome (HR = 4.97 CI: 1.87-13.2, P = 0.001). The CESC patients were classified by the median risk score. Immune infiltration analysis revealed significant increases in CD4 + Tcm, eosinophils, epithelial cells, fibroblasts, NKT, plasma cells, platelets, and smooth muscle in the high-risk group (P< 0.05). Target lncRNAs also showed some correlation with NRGs. The estimated IC50 values of bicalutamide, CHIR.99021, and imatinib were lower in the high-risk group. Through the subsequent experimental validation, both AC009095.1 and AC005332.4 were significantly more highly expressed in SiHa than in Hela. AC009095.1 was expressed more highly in SiHa than in HUCEC, but the expression of AC005332.4 was reversed.ConclusionsThis study elucidated that NRLs, as a novel signature, were indispensable factors which can significantly influence the prognosis of patients with CESC and could provide novel clinical evidence to serve as a potential molecular biomarker for future therapeutic targets.