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首页> 外文期刊>Glycobiology. >Molecular mechanism of anticancer effect of Sclerotium rolfsii lectin in HT29 cells involves differential expression of genes associated with multiple signaling pathways: A microarray analysis
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Molecular mechanism of anticancer effect of Sclerotium rolfsii lectin in HT29 cells involves differential expression of genes associated with multiple signaling pathways: A microarray analysis

机译：罗氏菌凝集素在HT29细胞中抗癌作用的分子机制涉及与多个信号通路相关的基因的差异表达：微阵列分析

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Sclerotium rolfsii lectin (SRL) is a lectin isolated from fungus S. rolfsii and has high binding specificity toward the oncofetal Thomsen-Friedenreich carbohydrate antigen (Gal beta 1-3GalNAc-alpha-O-Ser/Thr, T or TF), which is expressed in more than 90% of human cancers. Our previous studies have shown that binding of SRL to human colon, breast and ovarian cancer cells induces cell apoptosis in vitro and suppresses tumor growth in vivo. This study investigated the SRL-mediated cell signaling in human colon cancer HT29 cells by mRNA and miRNA microarrays. It was found that SRL treatment results in altered expression of several hundred molecules including mitogen-activated protein kinase (MAPK) and c-JUN-associated, apoptosis-associated and cell cycle and DNA replication-associated signaling molecules. Pathway analysis using GeneSpring 12.6.1 revealed that SRL treatment induces changes of MAPK and c-JUN-associated signaling pathways as early as 2 h while changes of cell cycle, DNA replication and apoptosis pathways were significantly affected only after 24 h. A significant change of cell miRNA expression was also observed after 12 h treatment of the cells with SRL. These changes were further validated by quantitative real time polymerase chain reaction and immunoblotting. This study thus suggests that the presence of SRL affects multiple signaling pathways in cancer cells with early effects on cell proliferation pathways associated with MAPK and c-JUN, followed by miRNA-associated cell activity and apoptosis. This provides insight information into the molecular mechanism of the anticancer activity of this fungal lectin.
机译：菌核罗勒菌凝集素（SRL）是从真菌S. rolfsii分离而来的凝集素，对胎粪中的Thomsen-Friedenreich碳水化合物抗原（Gal beta 1-3GalNAc-alpha-O-Ser / Thr，T或TF）具有很高的结合特异性在90％以上的人类癌症中都有表达。我们以前的研究表明，SRL与人结肠癌，乳腺癌和卵巢癌细胞的结合可在体外诱导细胞凋亡并在体内抑制肿瘤生长。这项研究通过mRNA和miRNA微阵列研究了人类结肠癌HT29细胞中SRL介导的细胞信号传导。发现SRL治疗导致数百个分子的表达改变，包括促分裂原活化蛋白激酶（MAPK）和c-JUN相关，凋亡相关以及细胞周期和DNA复制相关信号分子。使用GeneSpring 12.6.1进行的途径分析表明，SRL处理最早可在2 h时诱导MAPK和c-JUN相关信号通路的变化，而细胞周期，DNA复制和凋亡途径的变化仅在24 h后才受到显着影响。用SRL处理细胞12小时后，还观察到细胞miRNA表达的显着变化。通过实时定量聚合酶链反应和免疫印迹进一步验证了这些变化。因此，这项研究表明，SRL的存在会影响癌细胞中的多个信号传导途径，并对与MAPK和c-JUN相关的细胞增殖途径产生早期影响，随后是与miRNA相关的细胞活性和细胞凋亡。这提供了关于这种真菌凝集素抗癌活性的分子机制的深入信息。

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