Hepatocellular carcinoma (HCC) is the most common form of liver cancer. Because of the relatively chemotherapy-refractory nature of HCC and significant potential poor hepatic reserve, chemotherapy has not been used consistently in the treatment of HCC. Effective new drugs for HCC are urgently needed. Teriflunomide, which was approved for the treatment of relapsing forms of multiple sclerosis (MS), has been identified as a potential antineoplastic drug. Long noncoding RNAs (lncRNAs) are a novel class of RNA molecules defined as transcripts longer than 200 nucleotides that lack protein coding potential. In this study, we investigated the ability of teriflunomide to act as an antineoplastic drug by examining the effects of teriflunomide treatment on HCC cells. Teriflunomide strongly inhibited the proliferation of HCC cells, induced cell apoptosis and induced cell accumulation in S phases of the cell cycle. LncRNA and mRNA expression profiles of HCC cells treated with teriflunomide compared with controls were performed by using microarray analysis. For comparison, the differentially expressed mRNAs were annotated by using gene ontology (GO) and pathway analyses. The microarray revealed that 2085 lncRNAs and 1561 mRNAs differed in the cells treated with teriflunomide compared with controls. Several GO terms including protein folding, mitochondrial outer membrane, transmembrane receptor protein phosphatase activity, negative regulation of cellular biosynthetic process, DNA packaging complex, and receptor signaling protein activity were enriched in gene lists, suggesting a potential correlation with the action mechanism of teriflunomide. Pathway analysis then demonstrated that JAK-STAT signaling pathway may play important roles in the cell apoptosis induced by teriflunomide. Co-expression network analysis indicated that a number of lncRNAs and mRNAs were included in the co-expression network, and p34710_v4 is the lncRNA with highest degree. Then the mRNAs associated with those differentially expressed lncRNAs were also annotated by using gene ontology (GO) and pathway analyses. The pathway analyses shows that teriflunomide significantly inhibited cell proliferation and promoted cell apoptosis partly by participating in Wnt signaling pathways. These findings suggest that teriflunomide could be a potential drug for chemotherapy and molecularly targeted therapies of HCC.

肝细胞癌（HCC）是最常见的肝癌形式。由于肝癌的相对化疗难治性和明显的潜在肝储备不足，化学治疗一直未在肝癌的治疗中持续使用。迫切需要有效的HCC新药。特立氟胺已被批准用于治疗复发性多发性硬化症（MS），已被确认为潜在的抗肿瘤药。长非编码RNA（lncRNA）是一类新颖的RNA分子，其定义为缺少蛋白质编码潜力的长于200个核苷酸的转录本。在这项研究中，我们通过检查特立氟胺治疗对HCC细胞的作用，研究了特立氟胺作为抗肿瘤药的能力。teriflunomide强烈抑制HCC细胞的增殖，在细胞周期的S期诱导细胞凋亡和诱导细胞蓄积。通过使用微阵列分析，与对照相比，用特氟米特处理的HCC细胞的LncRNA和mRNA表达谱。为了进行比较，通过使用基因本体论（GO）和途径分析来注释差异表达的mRNA。微阵列显示，与对照组相比，特立氟胺处理的细胞中有2085个lncRNA和1561个mRNA不同。基因列表中丰富了蛋白质折叠，线粒体外膜，跨膜受体蛋白磷酸酶活性，细胞生物合成过程的负调控，DNA包装复合物和受体信号蛋白活性等几个GO术语，表明与teriflunomide的作用机理可能存在相关性。然后，通路分析表明，JAK-STAT信号通路可能在特立氟胺诱导的细胞凋亡中起重要作用。共表达网络分析表明，共表达网络中包含许多lncRNA和mRNA，其中p34710_v4是表达度最高的lncRNA。然后，还使用基因本体论（GO）和途径分析来注释与那些差异表达的lncRNA相关的mRNA。通路分析表明，特立氟胺部分参与Wnt信号通路可显着抑制细胞增殖并促进细胞凋亡。这些发现表明，teriflunomide可能是用于HCC化疗和分子靶向治疗的潜在药物。共表达网络分析表明，共表达网络中包含许多lncRNA和mRNA，其中p34710_v4是表达度最高的lncRNA。然后，还使用基因本体论（GO）和途径分析来注释与那些差异表达的lncRNA相关的mRNA。通路分析表明，特立氟胺部分参与Wnt信号通路可显着抑制细胞增殖并促进细胞凋亡。这些发现表明，teriflunomide可能是用于HCC化疗和分子靶向治疗的潜在药物。共表达网络分析表明，共表达网络中包含许多lncRNA和mRNA，其中p34710_v4是表达度最高的lncRNA。然后，还使用基因本体论（GO）和途径分析来注释与那些差异表达的lncRNA相关的mRNA。通路分析表明，特立氟胺部分参与Wnt信号通路可显着抑制细胞增殖并促进细胞凋亡。这些发现表明，teriflunomide可能是用于HCC化疗和分子靶向治疗的潜在药物。然后，还使用基因本体论（GO）和途径分析来注释与那些差异表达的lncRNA相关的mRNA。通路分析表明，特立氟胺部分参与Wnt信号通路可显着抑制细胞增殖并促进细胞凋亡。这些发现表明，teriflunomide可能是用于HCC化疗和分子靶向治疗的潜在药物。然后，还使用基因本体论（GO）和途径分析来注释与那些差异表达的lncRNA相关的mRNA。通路分析表明，特立氟胺部分参与Wnt信号通路可显着抑制细胞增殖并促进细胞凋亡。这些发现表明，teriflunomide可能是用于HCC化疗和分子靶向治疗的潜在药物。