溶质载体家族25成员21(solute carrier 25 member 21,SLC25A21)是氧代二羧酸盐载体,其主要功能是通过反向交换机制将胞浆内的2-氧代己二酸转运至线粒体。前期研究发现,在过表达SLC25A21的3T3-L1细胞中葡萄糖消耗能力显著增加。为进一步...溶质载体家族25成员21(solute carrier 25 member 21,SLC25A21)是氧代二羧酸盐载体,其主要功能是通过反向交换机制将胞浆内的2-氧代己二酸转运至线粒体。前期研究发现,在过表达SLC25A21的3T3-L1细胞中葡萄糖消耗能力显著增加。为进一步挖掘SLC25A21下游关键代谢基因,本研究在3T3-L1细胞中上调SLC25A21表达,利用高通量测序结合生物信息学分析获得差异表达基因,并通过实时荧光定量聚合酶链式反应(quantitative real-time polymerase chain reaction,qRT-PCR)验证关键基因表达。结果显示:(1)过表达SLC25A21的脂肪细胞中有26个上调基因,66个下调基因;(2)基因本体论(gene ontology,GO)分析表明,差异表达基因的生物学功能主要涉及脂质合成和代谢过程;京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)和基因集富集分析(gene set enrichment analysis,GSEA)表明,差异表达基因主要富集在鞘脂代谢、胰岛素和胰高血糖素样肽1分泌和合成等信号通路;(3)CytoHubba筛选出GRB2、SOS1、SHC1、CBL、HRAS、SOS2、EGFR、MET、PLCG2和KRAS等10个评分最高的关键基因,主要参与了细胞的糖、脂代谢过程;(4)在脂肪细胞中过表达SLC25A21,qRT-PCR验证结果表明除KRAS表达无明显变化外,其余基因的mRNA表达水平均出现相应的增高。本研究结果将为今后深入研究SLC25A21在糖、脂代谢过程中的作用及机制提供理论依据。展开更多
Objective To observe the effect of artesunate (Art) on the proliferation of human esophageal carcinoma cell line Eca109 and the growth of transplantation tumors of nude mice, and explore the possible involvement of CD...Objective To observe the effect of artesunate (Art) on the proliferation of human esophageal carcinoma cell line Eca109 and the growth of transplantation tumors of nude mice, and explore the possible involvement of CDC25A expression in the cell cycle arrest induced by Art. Methods MTT method was employed to detect the proliferation of the Eca109 cells and normal human peripheral blood mononuclear cells (hPBMC) after Art treatment. Cell cycle of the tumor cells was assayed by flow cytometry. Inhibitory effects of Art on the transplanted tumor on nude mice were observed by mass weight, volume and morphological method. The expression of CDC25A in the Eca109 cells was examined by RT-PCR and Western blotting. Results Art significantly inhibited the proliferation of Eca109 with the IC50 of (68.80±0.76) μmol/L, while it had weaker effect on that of the hPBMC induced by Con A. At lower doses of Art, the number of Eca109 cells during G0/G1 was increased, and that at S phase was reduced dramatically. However, when the concentration was up to 100 μmol/L, most of cells were arrested at G2/M phase. The volume and weight of transplanted tumor receiving Art treatment were smaller and lower than those of control group, with the maximal inhibitory rate of 76.4%. Art dramatically inhibited the mRNA as well as protein expressions of CDC25A in the Eca109 cells. Conclusion Art can inhibit the proliferation of tumor cells and transplanted tumor without apparent side effect, possibly by the mechanism of modulating cell cycle through CDC25A down-regulation.展开更多
文摘溶质载体家族25成员21(solute carrier 25 member 21,SLC25A21)是氧代二羧酸盐载体,其主要功能是通过反向交换机制将胞浆内的2-氧代己二酸转运至线粒体。前期研究发现,在过表达SLC25A21的3T3-L1细胞中葡萄糖消耗能力显著增加。为进一步挖掘SLC25A21下游关键代谢基因,本研究在3T3-L1细胞中上调SLC25A21表达,利用高通量测序结合生物信息学分析获得差异表达基因,并通过实时荧光定量聚合酶链式反应(quantitative real-time polymerase chain reaction,qRT-PCR)验证关键基因表达。结果显示:(1)过表达SLC25A21的脂肪细胞中有26个上调基因,66个下调基因;(2)基因本体论(gene ontology,GO)分析表明,差异表达基因的生物学功能主要涉及脂质合成和代谢过程;京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)和基因集富集分析(gene set enrichment analysis,GSEA)表明,差异表达基因主要富集在鞘脂代谢、胰岛素和胰高血糖素样肽1分泌和合成等信号通路;(3)CytoHubba筛选出GRB2、SOS1、SHC1、CBL、HRAS、SOS2、EGFR、MET、PLCG2和KRAS等10个评分最高的关键基因,主要参与了细胞的糖、脂代谢过程;(4)在脂肪细胞中过表达SLC25A21,qRT-PCR验证结果表明除KRAS表达无明显变化外,其余基因的mRNA表达水平均出现相应的增高。本研究结果将为今后深入研究SLC25A21在糖、脂代谢过程中的作用及机制提供理论依据。
文摘Objective To observe the effect of artesunate (Art) on the proliferation of human esophageal carcinoma cell line Eca109 and the growth of transplantation tumors of nude mice, and explore the possible involvement of CDC25A expression in the cell cycle arrest induced by Art. Methods MTT method was employed to detect the proliferation of the Eca109 cells and normal human peripheral blood mononuclear cells (hPBMC) after Art treatment. Cell cycle of the tumor cells was assayed by flow cytometry. Inhibitory effects of Art on the transplanted tumor on nude mice were observed by mass weight, volume and morphological method. The expression of CDC25A in the Eca109 cells was examined by RT-PCR and Western blotting. Results Art significantly inhibited the proliferation of Eca109 with the IC50 of (68.80±0.76) μmol/L, while it had weaker effect on that of the hPBMC induced by Con A. At lower doses of Art, the number of Eca109 cells during G0/G1 was increased, and that at S phase was reduced dramatically. However, when the concentration was up to 100 μmol/L, most of cells were arrested at G2/M phase. The volume and weight of transplanted tumor receiving Art treatment were smaller and lower than those of control group, with the maximal inhibitory rate of 76.4%. Art dramatically inhibited the mRNA as well as protein expressions of CDC25A in the Eca109 cells. Conclusion Art can inhibit the proliferation of tumor cells and transplanted tumor without apparent side effect, possibly by the mechanism of modulating cell cycle through CDC25A down-regulation.
