Genome-wide analysis of miRNA signature differentially expressed in doxorubicin-resistant and parental human hepatocellular carcinoma cell lines.
Genome-wide analysis of miRNA signature differentially expressed in doxorubicin-resistant and parental human hepatocellular carcinoma cell lines.
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对阿霉素耐药细胞系和亲代人肝细胞癌细胞系中差异表达的 miRNA 特征进行全基因组分析。
DOI：
10.1371/journal.pone.0054111
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wan J
中科院分区：
文献类型：
--
作者：
Zhang J;Wang Y;Zhen P;Luo X;Zhang C;Zhou L;Lu Y;Yang Y;Zhang W;Wan J
化疗方案已广泛用于治疗多种人类恶性肿瘤，包括肝细胞癌（HCC）。化疗失败的一个主要原因是癌细胞的耐药性。对阿霉素（DOX）的耐药性是有效治疗癌症的常见且具有代表性的障碍。最近的研究已将个体 microRNA (miRNA) 引入到 HCC 的 DOX 耐药性进化中。然而，仍然缺乏对导致 DOX 耐药性的 miRNA 表达谱进行全球和系统的评估。在本研究中，我们应用高通量 Illumina 测序来全面表征人 HCC 细胞系 (HepG2) 及其 DOX 耐药细胞系 (HepG2/DOX) 中的 miRNA 表达谱。共有269个已知miRNA在HepG2/DOX细胞中存在显着差异表达，其中23个上调，246个下调，表明其中部分可能参与DOX耐药的发生。此外，我们还鉴定了 9 个和 13 个在 HepG2/DOX 细胞中分别显着上调和下调表达的新 miRNA。然后通过定量实时 PCR 对选定的 miRNA（包括 22 种已知 miRNA 和 6 种新 miRNA）验证 miRNA 分析。此外，我们还预测了样品中失调的 miRNA 的假定靶基因。功能注释表明这些选定的miRNA影响了许多主要参与MAPK信号通路的靶基因。这项研究为我们提供了 miRNA 表达谱的一般描述，有助于寻找潜在的 miRNA 用于辅助治疗，以克服未来 HCC 化疗中的 DOX 耐药性。
Chemotherapy regiments have been widely used in the treatment of a variety of human malignancies including hepatocellular carcinoma (HCC). A major cause of failure in chemotherapy is drug resistance of cancer cells. Resistance to doxorubicin (DOX) is a common and representative obstacle to treat cancer effectively. Individual microRNA (miRNA) has been introduced in the evolution of DOX resistance in HCC in recent studies. However, a global and systematic assessment of the miRNA expression profiles contributing to DOX resistance is still lacking. In the present study, we applied high-throughput Illumina sequencing to comprehensively characterize miRNA expression profiles in both human HCC cell line (HepG2) and its DOX-resistant counterpart (HepG2/DOX). A total of 269 known miRNAs were significantly differentially expressed, of which 23 were up-regulated and 246 were down-regulated in HepG2/DOX cells, indicating that part of them might be involved in the development of DOX resistance. In addition, we have identified 9 and 13 novel miRNAs up- and down-expressed significantly in HepG2/DOX cells, respectively. miRNA profiling was then validated by quantitative real-time PCR for selected miRNAs, including 22 known miRNAs and 6 novel miRNAs. Furthermore, we predicted the putative target genes for the deregulated miRNAs in the samples. Function annotation implied that these selected miRNAs affected many target genes mainly involved in MAPK signaling pathway. This study provides us a general description of miRNA expression profiling, which is helpful to find potential miRNAs for adjunct treatment to overcome DOX resistance in future HCC chemotherapy.
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