• Artificial intelligence
• Hepatocellular carcinoma
• Prognosis

• biomarkers
• hepatocellular carcinoma
• non-targeted metabolomics
• serum exosomes

• H2022329002 Natural Science Foundation of Hebei Province

• biomarkers
• hepatocellular carcinoma
• metabolomics
• multi-omics
• precision medicine

• ferroptosis
• glutathione
• hepatocellular carcinoma (HCC)
• lipid peroxidation
• parthenolide (PTL)
• thiol oxidation

• P20 GM109005 NIGMS NIH HHS
• R01 CA258673 NCI NIH HHS
• T32 GM106999 NIGMS NIH HHS
• University of Arkansas for Medical Sciences
• National Institute of General Medical Sciences
• Translational Research Institute, University of Arkansas for Medical Sciences

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.

To investigate the tumorigenic role of spen paralogue and orthologue C-terminal domain-containing 1 (SPOCD1) in hepatocellular carcinoma (HCC) and identify the upstream regulatory mechanism.

We analyzed SPOCD1 and miR-133-3p expression in normal and HCC tissues from the Cancer Genome Atlas and UALCAN databases, and in normal hepatocytes and HCC cell lines by real-time quantitative polymerase chain reaction and western blot. We identified the miR-133a-3p-binding site on the SPOCD1 3ʹ-untranslated region using TargetScan. Hierarchical regulation was confirmed by luciferase assay and miR-133a-3p overexpression/silencing. Cell proliferation, migration, invasion, and colony formation were assessed by MTT, scratch, transwell, and clonogenic assays, respectively.

SPOCD1 was highly expressed in HCC tissues and cell lines, while miR-133a-3p expression was significantly downregulated. Kaplan–Meier analysis indicated that high SPOCD1 expression was significantly associated with poor survival. TargetScan and luciferase reporter assay revealed that SPOCD1 was the downstream target of miR-133a-3p. Overexpression of miR-133a-3p significantly inhibited the expression of SPOCD1, while miR-133a-3p knockdown significantly increased SPOCD1 expression.

SPOCD1, regulated by miR-133a-3p, promotes HCC cell proliferation, migration, invasion, and colony formation. This study provides the first evidence for the role of the miR-133a-3p/SPOCD1 axis in HCC tumorigenesis.

• Egypt
• Hepatitis B virus
• Hepatitis C virus
• Hepatocellular carcinoma
• Liver cancer
• Screening

Objective: This study intends to identify potential prognostic marker genes associated with the prognosis of patients suffering from hepatocellular carcinoma (HCC) based on TCGA and GEO analysis.

Methods: TCGA-LIHC cohort was downloaded and the data related to HCC were extracted from The Cancer Genome Atlas (TCGA) database and subjected to differential analysis. HCC-related gene expression datasets were retrieved from the GEO database, followed by differential analysis. After intersection of the results of TCGA and GEO databases, gene interaction analysis was performed to obtain the core genes. To identify the genes related to the prognosis of HCC patients, we conducted univariate and multivariate Cox analyses.

Results: Based on differential analysis of TCGA database, 854 genes were differentially expressed in HCC, any of which might link to the occurrence and progression of HCC. Meanwhile, joint analysis of HCC-related gene expression datasets in the GEO database screened 214 genes. Five core genes CDC20, TOP2A, RRM2, UBE2C and AOX1 were significantly associated with the prognosis of HCC patients and the risk model based on these five genes effectively predicted the prognosis of HCC patients.

Conclusion: Collectively, our data suggest that CDC20, TOP2A, RRM2, UBE2C and AOX1 may be the key genes affecting the prognosis of patients with HCC. The five-gene signature could accurately predict the prognosis of HCC patients.

• AOX1
• CDC20
• RRM2
• TOP2A
• UBE2C
• hepatocellular carcinoma
• immune cells
• multi-databases-based joint analysis

Circular RNAs (circRNAs) could interact with miRNAs to regulate gene expression, participating in hepatocellular carcinoma (HCC) initiation and development. This work aimed to determine the potential function and molecular mechanism of circEPB41L2 (hsa_circ_0077837) during HCC progression.

The expression of circEPB41L2 in HCC tissues and HCC cell lines was quantified using real-time quantitative PCR (qRT-PCR). CCK-8 assays and colony formation assays were utilized to detect the proliferation of HCC cells. Wound healing assay and transwell assay were performed to determine the capability of migration and invasion for HCC cells. Western blot was conducted to determine gene expression on protein levels. The effect of circEPB41L2 on HCC in vivo was investigated via xenograft experiment. Interaction between circEPB41L2 and miR-590-5p was predicted through bioinformatics methods and confirmed via luciferase reporter assay.

Extensive analysis of circRNA profiles in tumor and matched para-tumor tissues collected from 61 HCC patients identified that circEPB41L2 was significantly down-regulated in HCC, which was further confirmed in another HCC group by qRT-PCR analysis. The clinicopathological analysis revealed that down-regulation of circEPB41L2 was negatively associated with tumor size, vascular invasion and alpha-fetoprotein, while positively correlated with HCC prognosis. The biological function experiments showed that overexpression of circEPB41L2 could obviously inhibit the proliferation and metastasis of HCC cells in vitro, while knockdown of circEPB41L2 induced opposite results. Moreover, we also found that circEPB41L2 inhibited HCC migration and invasion though EMT signaling pathway. Similarly, overexpression of circEPB41L2 can also significantly inhibit the proliferation of HCC cells in vivo. Bioinformatic analysis and luciferase reporter assay revealed that circEPB41L2 interacts directly with miR-590-5p and the corresponding biological functions were also verified in miRNA rescue experiments.

Our results suggest that circEPB41L2 might function as a tumor suppressor during HCC progression by sponging miR-590-5p.

• circEPB41L2
• circular RNA
• hepatocellular carcinoma
• miR-590-5p