Effect of OSW-1 on microRNA expression profiles of hepatoma cells and functions of novel microRNAs

Effect of OSW-1 on microRNA expression profiles of hepatoma cells and functions of novel microRNAs
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OSW-1对肝癌细胞microRNA表达谱及新型microRNA功能的影响

DOI:
10.3892/mmr.2013.1428
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发表时间:
2013-06-01
影响因子:
3.4
通讯作者:
Liu, Shuang-Ping
Liu, Shuang-Ping
中科院分区:
医学4区
文献类型:
--
作者:
Jin, Ji-Chun;Jin, Xing-Lin;Liu, Shuang-Ping

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3-β,16-β,17-三羟基胆甾酮-5-烯-22-酮(16-O-(2-O-4-methoxybenzoyl-beta-D-xylopyranosyl)-(1->3)-(2-O-乙酰基-α-L-阿拉伯吡喃糖苷)(Osw-1)是胆甾烷皂苷家族的一员,最早从虎眼兰的鳞茎中分离得到,先前报道对多种类型的恶性肿瘤具有细胞毒作用。然而,其抗肿瘤机制尚不清楚。因此,我们研究了microRNA(MiRNA)的表达谱,以探索OSW-1的抗肿瘤活性。此外,在对差异表达的miRNAs进行研究之后,利用已知的miRNAs和抗癌药物确定了新的miRNAs和OSW-1的功能。目前的研究表明,OSW-1治疗导致一大批与肿瘤相关的miRNAs表达上调和下调,包括miR-299、miR-1908、miR-125b、miR-187a、miR-1275、HAV1-miR-H6-3p、miR-181、miR-210、miR-483、miR-126、miR-208等。值得注意的是,与单独使用阿霉素相比,OSW-1和阿霉素上调了miR-141、miR-142、miR-200C和miR-1275。此外,miR-142-3P的表达倍数变化类似于不同处理的58倍。这些miRNAs与癌症有关,包括增殖、分化、凋亡、细胞黏附、迁移、极性和上皮细胞向间充质细胞的转变(EMT)。
3 beta,16 beta,17 alpha-trihydroxycholest-5-en-22-one 16-O-(2-O-4-methoxybenzoyl-beta-D-xylopyranosyl)-(1 -> 3)-(2-O-acetyl-alpha-L-arabinopyranoside) (OSW-1) is a member of the cholestane saponin family, which was first isolated from the bulbs of Ornithogalum saundersiae and previously reported to be cytotoxic against several types of malignant cells. However, its antitumor mechanism remains unclear. Therefore, we investigated microRNA (miRNA) expression profiles in order to explore the antitumor activities of OSW-1. Furthermore, following study of differentially expressed miRNAs, the function of novel miRNAs and OSW-1 was determined using known miRNAs and anticarcinogens. The present study demonstrated that treatment with OSW-1 leads to the upregulation and downregulation of a large set of tumor-related miRNAs, including miR-299, miR-1908, miR-125b, miR-187a, miR-1275, hav1-miR-H6-3p, miR-181, miR-210, miR-483, miR-126, miR-208 and others. Notably, miR-141, miR-142, miR-200C and miR-1275 were found to be upregulated by OSW-1 and doxorubicine, as compared with doxorubicine alone. Additionally, the expression fold-change of miR-142-3P was similar to 58 times higher than its expression with a different treatment. These miRNAs are linked to cancer, including proliferation, differentiation, apoptosis, cell adhesion, migration, polarity and epithelial to mesenchymal transition (EMT).