Role of microRNA-95 in the anticancer activity of Brucein D in hepatocellular carcinoma

Role of microRNA-95 in the anticancer activity of Brucein D in hepatocellular carcinoma
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microRNA-95在Brucein D抗肝细胞癌活性中的作用

DOI:
10.1016/j.ejphar.2014.02.002
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发表时间:
2014-04-05
影响因子:
5
通讯作者:
Chen, Yangchao
Chen, Yangchao
中科院分区:
医学2区
文献类型:
--
作者:
Xiao, Zhangang;Chow, Sheung Ching;Chen, Yangchao

文献摘要

被引文献

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鸦胆子(Brucea javanica)果实被用于治疗阿米巴痢疾、疟疾和各种寄生虫,并在传统中药中被用作抗癌剂,鸦胆子素D(Brucein D,BD)是从鸦胆子果实中提取的天然化合物,具有抗胰腺癌的活性。在这里,我们进一步证明,BD抑制肝细胞癌(HCC)细胞生长在体外和肿瘤生长在体内归因于诱导细胞凋亡。BD对非致瘤性人肝细胞没有生长抑制作用。MTT法检测细胞膜联蛋白V(AnnexinV)含量,TUNEL法检测细胞悬液和组织切片中的凋亡细胞。筛选出BD的下游micro-RNA(miRNA)靶标。miRNA阵列通过生物信息学分析和荧光素酶报告基因分析鉴定miRNAs及其大探针。共鉴定出39个BD调控的miRNAs,其中miR-95是BD潜在的靶向药物。我们进一步鉴定了CUG三联体。将RNA结合蛋白2(CUGBP 2)作为miR-95的下游较大者。我们的数据表明,BD通过调节miR-95的表达而发挥抗肝癌活性。(C)2014爱思唯尔有限公司版权所有。
Brucea javanica fruit has been used to treat amebic dysentery, malaria and various parasites and it has been applied as an anti cancer agent in Traditional Chinese Medicine, Brucein D (BD) is a naturally occurring compound extracted from Brucea javanica fruit which shows anti cancer activity against pancreatic cancer. Here, we further demonstrated that BD inhibited hepatocellular carcinoma (HCC) cell growth in vitro and tumor growth in vivo that were attributed to the induction of cell apoptosis. BD did not exert growth inhibition on non-tumorigenic human hepatocytes. MTT assay was used to measure cell Annexin V and TUNEL assay were applied To identify apoptotic cells in cell suspension and in Tissue section respectively. Downstream micro-RNA (miRNA) targets of BD were screened out. by miRNA array. miRNAs and their Larger prole ins were identified by bioinformatics analysis and luciferase reporter assay. 39 miRNAs regulated by BD in HCC were identified, miR-95 was found To be a potential drug Larger of BD. We further identified CUG Triplet. repeal RNA binding protein 2 (CUGBP2) as the downstream Larger of miR-95. Our data suggested that BD exerted as anti-cancer activity against HCC through modulation of miR-95 expression. (C) 2014 Elsevier B.V. All rights reserved.