CCNB1 promotes the development of hepatocellular carcinoma by mediating DNA replication in the cell cycle.

In our studies, cyclin B1 (CCNB1) mRNA and protein were overexpressed in hepatocellular carcinoma (HCC) tissues compared with non-HCC tissues. Moreover, CCNB1 was overexpressed in the serum of HCC patients. The expression of CCNB1 was associated with several crucial clinicopathologic characteristics, and the HCC patients with overexpressed CCNB1 had worse overall survival outcomes. In the screening of interactional genes, a total of 266 upregulated co-expression genes, which were positively associated with CCNB1, were selected from the datasets, and 67 downregulated co-expression genes, which were negatively associated with CCNB1, were identified. The key genes might be functionally enriched in DNA replication and the cell cycle pathways. CDC20, CCNA2, PLK1, and FTCD were selected for further research because they were highly connected in the protein-protein interaction networks. Upregulated CDC20, CCNA2, and PLK1 and downregulated FTCD might result in undesirable overall survival outcomes for HCC patients. The univariate Cox analysis results showed that CDC20 and PLK1 might be two independent risk factors, while FTCD might be protective in HCC. Therefore, CCNB1 may participate in the cell cycle of HCC by regulating DNA replication, and CCNB1 may provide a direction for the diagnosis of early-stage HCC and targeted HCC therapy.

Identification of prognostic splicing factors and exploration of their potential regulatory mechanisms in pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PAAD), the most common subtype of pancreatic cancer, is a highly lethal disease. In this study, we integrated the expression profiles of splicing factors (SFs) of PAAD from RNA-sequencing data to provide a comprehensive view of the clinical significance of SFs. A prognostic index (PI) based on SFs was developed using the least absolute shrinkage and selection operator (LASSO) COX analysis. The PI exhibited excellent performance in predicting the status of overall survival of PAAD patients. We also used the percent spliced in (PSI) value obtained from SpliceSeq software to quantify different types of alternative splicing (AS). The prognostic value of AS events was explored using univariate COX and LASSO COX analyses; AS-based PIs were also proposed. The integration of prognosis-associated SFs and AS events suggested the potential regulatory mechanisms of splicing processes in PAAD. This study defined the markedly clinical significance of SFs and provided novel insight into their potential regulatory mechanisms.

Overexpression of MiR-452-5p in hepatocellular carcinoma tissues and its prospective signaling pathways.

BACKGROUND: The implication of miR-452-5p and its prospective machinery in hepatocellular carcinoma (HCC) remains largely unknown. For this reason, this study aimed to inspect the clinical implication of miR-452-5p expression in HCC tissues with multiple detection approaches, to analyze its potential function via in silico methods, and to validate this using a dual-luciferase reporter assay. METHODS: The assessment of the expression level of miR-452-5p in HCC was conducted via four methods: 1) in-house real-time quantitative PCR (RT-qPCR), 2) miRNA-sequencing (miRNA-seq) from The Cancer Genome Atlas (TCGA), 3) miRNA microarrays from the Gene Expression Omnibus (GEO), and 4) comprehensive meta-analyses calculating the standard mean difference (SMD) and summary of receiver operator characteristic (sROC). Following the target prediction, one of the potential targets of miR-452-5p was validated through a dual-luciferase reporter assay. RESULTS: MiR-452-5p was consistently elevated in HCC tissues via various detection methods, including in-house RT-qPCR, miRNA-seq, and miRNA microarrays. The final SMD was 0.842 for 820 cases of HCC samples. Simultaneously, the area under curve (AUC) of the sROC was 0.80 (0.76-0.83). The 1,135 predicted targets of miR-452-5p were enriched in the pathways of cytokine-cytokine receptor interaction, carbon metabolism, and complement and coagulation cascades. Among these predicted targets, CDKN1B was verified to be a real target of miR-452-5p. CONCLUSION: The overexpression of miR-452-5p may play a pivotal role in the carcinogenesis of HCC via targeting multiple signaling pathways and genes. The function and molecular machinery of miR-452-5p in HCC requires further in-depth exploration.