Abstract
Background: More and more studies show that long non-coding RNAs (lncRNAs) have miniature open reading frames that can be translated into short peptides. Here, we identify the long non-coding gene LINC00665 and its short peptides (CIP2A-BP) in hepatocellular carcinoma (HCC) and explore how they contribute to HCC progression. Materials and methods: First, GSE101728 data were acquired through the Gene Expression Omnibus for identification of differentially expressed genes (DEGs), and gene set enrichment analysis (GSEA) was conducted to find enriched biological pathways. Then, further bioinformatics analysis was carried out on the screened long non-coding genes, and LINC00665 expression was detected in HCC and normal liver samples. The relations between LINC00665 expression, HCC prognosis, and clinical characteristics were studied. Receiver operating characteristic (ROC) analysis was also applied to verify the LINC00665 prediction in HCC prognosis. In addition, pertinent experiments on LINC00665 and CIP2A-BP were also carried out to explore their roles in the progression of HCC. Results: As a result, we screened out 332 DEGs in total, including 130 upregulated and 202 downregulated DEGs. These DEGs were mainly enriched in posttranscriptional regulation of gene expression, RNA processing, nucleolus, and gene silencing biological pathways. In addition, we found that LINC00665 was increased in HCC samples, which substantially indicated its poor prognosis. Compared with normal tissues, LINC00665 had higher expression in the pathological stages III and IV, tumor-free groups, people no more than 60 years old, and stages T3, T4, N0, N1, and M1. ROC curve indicated that the variable INC00665 had certain accuracy in predicting overall survival (OS). Moreover, in functional experiments, LINC00665 knockdown could significantly decrease HCC cell proliferation, migration, and invasion, while overexpressed CIP2A-BP could markedly increase HCC cell proliferation, invasion, and migration. Conclusion: Our findings not only disclose a unique mechanism by which CIP2A-BP encoded by LINC00665 promotes HCC carcinogenesis but suggest that these long non-coding genes and short peptides could be used as biomarkers for HCC diagnosis and prognosis and new targets for HCC therapy.
Highlights
More and more studies show that long non-coding RNAs have miniature open reading frames that can be translated into short peptides
DEG analysis was performed on the genes in these samples by the GEO2R tool, and the filtering condition for upregulated DEGs was set to a fold change (FC) > 2, and that for downregulated DEGs was FC < 0.5, both satisfying p < 0.001
After analyzing the long non-coding RNAs (lncRNAs) in the GSE101728 data set by the GEO2R method, we obtained 332 DEGs, of which 130 were upregulated and 202 were downregulated
Summary
More and more studies show that long non-coding RNAs (lncRNAs) have miniature open reading frames that can be translated into short peptides. Liver cancer (LC) is an extremely harmful malignant tumor in surgical diseases, which is generally divided into primary and secondary types (Sia et al, 2017). The former originates from the liver epithelial or mesenchymal tissues, including hepatocellular carcinoma (HCC), cholangiocarcinoma, and mixed liver cancer (Bosch et al, 1999; Bosch et al, 2004). The latter is formed by the metastasis of malignant tumors from the stomach, pancreas, biliary tract, and others to the liver (Ananthakrishnan et al, 2006). To prolong the survival time of patients and improve their life quality, there is an urgent need for the emergence of safe and effective anticancer technologies
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