Abstract
Increasing studies have reported that circular RNAs (circRNAs) play critical roles in tumorigenesis and cancer progression. However, the underlying regulatory mechanisms of circRNA-related competing endogenous RNA (ceRNA) in liver hepatocellular carcinoma (LIHC) are still unclear. In the present study, we discovered dysregulated circRNAs through Gene Expression Omnibus (GEO) analysis and validated the expression of the top seven circRNAs with upregulated expression by qRT–PCR and Sanger sequencing. Then, the Cancer-Specific CircRNA Database (CSCD) was used to predict the downstream miRNAs of seven circRNAs, and expression and survival analyses through The Cancer Genome Atlas (TCGA) were performed to identify the key miRNA in LIHC. Thereafter, the hsa_circ_0017264-hsa-miR-195–5p subnetwork was successfully constructed. Subsequently, we predicted downstream target genes of hsa-miR-195–5p with TargetScan, miRDB, and mirtarbase and overlapped them with differentially expressed mRNAs to obtain 21 target genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to predict the biological and functional roles of these target genes. Finally, with Pearson correlation and prognostic value analysis, a survival-related hsa_circ_0017264-hsa-miR-195-5p-CHEK1/CDC25A/FOXK1 axis was established. Gene set enrichment analysis (GSEA) was performed to determine the function of CHEK1/CDC25A/FOXK1 in the ceRNA network. Moreover, immune infiltration analysis revealed that the ceRNA network was markedly associated with the levels of multiple immune cell infiltrates, immune cell biomarkers and immune checkpoints. Overall, the hsa_circ_0017264-hsa-miR-195-5p-CHEK1/CDC25A/FOXK1 network might provide novel insights into the potential mechanisms underlying LIHC onset and progression.
Highlights
Liver cancer is one of the most common malignant tumors; 75%–85% of liver cancer cases are classified as hepatocellular carcinoma (LIHC), and 10%–15% are classified as intrahepatic cholangiocarcinoma (CHOL) (Sung et al, 2021)
To identify some potential circRNAs related to the progression of liver hepatocellular carcinoma (LIHC), we used the GSE164803 dataset in Gene Expression Omnibus (GEO) to analyze the differential expression of liver cancer tissues and adjacent tissues based on the criterion |log2FC| > 1, adjusted p < 0.05
Our goal is to explore prognostic biomarkers increased in LIHC patients, which will be useful in clinical detection and contribute to future drug therapies
Summary
Liver cancer is one of the most common malignant tumors; 75%–85% of liver cancer cases are classified as hepatocellular carcinoma (LIHC), and 10%–15% are classified as intrahepatic cholangiocarcinoma (CHOL) (Sung et al, 2021). Increasing evidence suggests that the occurrence and development of LIHC are associated with abnormal genetic changes and cancer-related signaling pathways, such as TERT, the WNT/βcatenin pathway, and the mTOR pathway (Li et al, 2020). It is of great significance to explore the molecular mechanisms of LIHC to identify novel diagnostic and prognostic targets. Several studies (Yao et al, 2019; He et al, 2021) have revealed that circRNAs play a pivotal role in the occurrence and development of LIHC through ceRNA networks. CircRNAs can be used as diagnostic or prognostic markers for LIHC patients (Wang et al, 2019; Chen et al, 2020). We built a circRNA–miRNA–mRNA network to further clarify the detailed mechanism of circRNAs in LIHC
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