Identification of miRNAs, mRNAs, lncRNAs, and circRNAs associated with hepatocellular carcinoma recurrence after interferon treatment.
Identification of miRNAs, mRNAs, lncRNAs, and circRNAs associated with hepatocellular carcinoma recurrence after interferon treatment.
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干扰素治疗后与肝细胞癌复发相关的 miRNA、mRNA、lncRNA 和 circRNA 的鉴定。
DOI：
10.23812/21-173-a
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发表时间：
2021-07
期刊：
影响因子：
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通讯作者：
Lu Wang
中科院分区：
文献类型：
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作者：
Weiping Zhu;Xigan He;Hongxu Zhu;Lingli Wang;Zhenhai Lin;Miao Wang;Lu Wang
为了研究干扰素-α（IFN-α）治疗肝细胞癌（HCC）的分子机制和预测疗效的分子标志物，从4例未接受治疗的HCC患者（对照组）的12个样本中筛选差异表达（DE）-miRNAs、-mRNAs、-lncRNAs和-circRNAs，4例接受过重组人干扰素a-2b治疗（病例1），4例接受重组人干扰素a-2b治疗后复发（病例2）。进行富集分析以确定DE-RNA的主要功能。我们还构建了蛋白质-蛋白质相互作用（PPI）和竞争性内源RNA（ceRNA）网络。此外，进行了系列聚类分析，以分析不同HCC组间基因表达的变化。此外，这些基因的表达在癌症基因组图谱（TCGA）数据库中得到了验证。在对照组与病例1组以及病例2组与病例1组之间，共获得36个联合DE-miRNAs、175个联合DE-mRNAs、65个联合DE-lncRNAs和52个联合DE-circRNAs。DE-mRNA主要表达于线粒体内膜。DE-circRNA主要富集在高尔基体中。ceRNA网络包含68个DE-mRNA、26个DE-miRNA、45个DE-lncRNA和23个DE-circRNA。共24个DE-miRNAs、175个DE-mRNAs、65个DE-lncRNAs和52个DE-circRNAs分别被分为8个谱。与肝癌预后显著相关的基因有26个（p < 0.05）。某些基因可用于预测IFN-α治疗HCC的疗效。本研究结果为进一步探讨IFN-α治疗肝癌的敏感性差异奠定了基础。
To study the molecular mechanism of interferon-alpha (IFN-α) in the treatment of hepatocellular carcinoma (HCC) and the molecular markers that can predict the therapeutic effect, differentially expressed (DE)-miRNAs, -mRNAs, -lncRNAs, and -circRNAs were screened between 12 samples collected from 4 patients who had not received treatment (control), 4 patients who had received recombinant human interferon a-2b treatment (case1), and 4 patients who had relapsed after receiving recombinant human interferon a-2b treatment (case2). Enrichment analyses were performed to determine the principal functions of the DE-RNAs. We also constructed protein-protein interactions (PPI) and competing endogenous RNA (ceRNA) networks. In addition, a series-cluster analysis was performed to analyze changes in gene expression across different groups of HCC. Furthermore, the expression of the genes were verified in the Cancer Genome Atlas (TCGA) database. A total of 36 union DE-miRNAs, 175 union DE-mRNAs, 65 union DE-lncRNAs, and 52 union DE-circRNAs were obtained between the control vs case1, and case2 vs case1 groups. DE-mRNAs were mainly involved in the mitochondrial inner membrane. DE-circRNAs were mainly enriched in the Golgi apparatus. ceRNA network contained 68 DE-mRNAs, 26 DE-miRNAs, 45 DE-lncRNAs, and 23 DE-circRNAs. A total of 24 DE-miRNAs, 175 DE-mRNAs, 65 DE-lncRNAs, and 52 DE-circRNAs were classified into eight profiles, respectively. A total of 26 genes showed a significant correlation with prognosis of HCC (p < 0.05). Some genes may be used to predict the efficacy of IFN-α in the treatment of HCC. The results may lay a foundation for investigating the different sensitivities of IFN-α in the treatment of HCC.