Li Yi-Ran, Zong Rui-Qing, Zhang Hong-Yan, Meng Xiao-Yan, Wu Fei-Xiang
Department of Intensive Care Medicine, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Naval Medical University, Shanghai, China.
Front Genet. 2022 Mar 8;13:861096. doi: 10.3389/fgene.2022.861096. eCollection 2022.
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. 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. 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. 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.
越来越多的研究表明，长链非编码RNA（lncRNAs）具有可被翻译成短肽的微型开放阅读框。在此，我们在肝细胞癌（HCC）中鉴定出长链非编码基因LINC00665及其短肽（CIP2A-BP），并探究它们如何促进HCC进展。首先，通过基因表达综合数据库获取GSE101728数据以鉴定差异表达基因（DEGs），并进行基因集富集分析（GSEA）以找出富集的生物学途径。然后，对筛选出的长链非编码基因进行进一步的生物信息学分析，并在HCC和正常肝脏样本中检测LINC00665的表达。研究了LINC00665表达、HCC预后和临床特征之间的关系。还应用受试者工作特征（ROC）分析来验证LINC00665在HCC预后中的预测作用。此外，还对LINC00665和CIP2A-BP进行了相关实验，以探究它们在HCC进展中的作用。结果，我们总共筛选出332个DEGs，包括130个上调的和202个下调的DEGs。这些DEGs主要富集在基因表达的转录后调控、RNA加工、核仁以及基因沉默生物学途径中。此外，我们发现LINC00665在HCC样本中表达增加，这充分表明其预后不良。与正常组织相比，LINC00665在病理分期III和IV期、无瘤组、年龄不超过60岁的人群以及T3、T4、N0、N1和M1期表达较高。ROC曲线表明变量INC00665在预测总生存期（OS）方面具有一定的准确性。此外，在功能实验中，敲低LINC00665可显著降低HCC细胞的增殖、迁移和侵袭，而过表达CIP2A-BP可显著增加HCC细胞的增殖、侵袭和迁移。我们的研究结果不仅揭示了LINC00665编码的CIP2A-BP促进HCC癌变的独特机制，还表明这些长链非编码基因和短肽可作为HCC诊断和预后的生物标志物以及HCC治疗的新靶点。
