Profiling of 95 microRNAs in pancreatic cancer cell lines and surgical specimens by real-time PCR analysis.

Profiling of 95 microRNAs in pancreatic cancer cell lines and surgical specimens by real-time PCR analysis.
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DOI:
10.1007/s00268-008-9833-0
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发表时间:
2009-04
影响因子:
2.6
通讯作者:
Chen, Changyi
Chen, Changyi
中科院分区:
医学3区
文献类型:
--
作者:
Zhang, Yuqing;Li, Min;Wang, Hao;Fisher, William E.;Lin, Peter H.;Yao, Qizhi;Chen, Changyi

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MicroRNAs (miRNAs)参与癌症的发病、凋亡和细胞生长,因此既可以作为肿瘤抑制因子,也可以作为致癌基因。然而,这些mirna在胰腺癌中的表达改变和作用在很大程度上是未知的。我们假设胰腺癌可能具有独特的miRNA谱,可能在胰腺癌的发生、进展、诊断和预后中发挥关键作用。采用实时RT-PCR分析95个miRNAs的差异表达。所有95种mirna都是基于它们与癌症生物学、细胞发育和细胞凋亡相关的潜在功能而选择的。将胰腺癌组织样本或癌细胞系的mirna表达归一化为U6 RNA,并与相对正常的胰腺组织或正常的人胰导管上皮(HPDE)细胞中的mirna表达进行比较。慢性胰腺炎患者的胰腺组织也被纳入分析。在初步分析中,与相对正常的胰腺组织和HPDE细胞相比,胰腺癌组织(n=5)和细胞系(n=3)中大多数95种mirna的表达发生了实质性变化。然而,每种胰腺癌组织或细胞类型与其他病例或细胞类型以及慢性胰腺炎组织具有本质不同的谱图,表明胰腺癌的个体多样性。对10株胰腺癌细胞系和17对胰腺癌/正常组织进行进一步分析。8种mirna在大多数胰腺癌组织和细胞系中显著上调,包括miR-196a、miR-190、miR-186、miR-221、miR-222、miR-200b、miR-15b和miR-95。这8个基因在正常对照和肿瘤细胞或组织之间的上调率为70% ~ 100%。胰腺癌样本中这些mirna的增加幅度为正常对照的3 - 2018倍。与相对正常的胰腺组织或细胞以及胰腺炎组织相比,胰腺癌组织或细胞系在个体基础上具有独特的miRNA谱图。8种mirna的上调发生在大多数胰腺癌组织和细胞类型中。这些mirna可能在胰腺癌发病机制中具有共同的途径。本研究可能为进一步研究mirna在胰腺癌发生、发展、诊断和预后中的功能作用提供有用的信息。
MicroRNAs (miRNAs) are involved in cancer pathogenesis, apoptosis and cell growth, thereby functioning as either tumor suppressors or oncogenes. However, expression alterations and roles of these miRNAs in pancreatic cancer are largely unknown. We hypothesize that pancreatic cancer may have a unique miRNA profile, which may play a critical role in pancreatic cancer development, progression, diagnosis and prognosis. Differential expression of 95 miRNAs was analyzed by real time RT-PCR using the QuantiMir System. All 95 miRNAs chosen for the array are based on their potential functions related to cancer biology, cell development and apoptosis. The expression of miRNAs for pancreatic cancer tissue samples or cancer cell lines was normalized to U6 RNA and compared with those in the relatively normal pancreatic tissues or normal human pancreatic ductal epithelial (HPDE) cells. Human pancreatic tissue with chronic pancreatitis was also included for analysis. In the initial analysis, the expression of most 95 miRNAs was substantially changed in pancreatic cancer tissues (n=5) and cell lines (n=3) compared with relatively normal pancreatic tissues and HPDE cells. However, each pancreatic cancer tissue or cell type had a substantially different profiling pattern with other cases or cell types as well as chronic pancreatitis tissue, indicating the individual diversity of pancreatic cancer. Further analysis was performed on 10 pancreatic cancer cell lines and 17 pairs of pancreatic cancer/normal tissues. Eight miRNAs were significantly upregulated in most pancreatic cancer tissues and cell lines, including miR-196a, miR-190, miR-186, miR-221, miR-222, miR-200b, miR-15b and miR-95. The incidence of upregulation of these eight genes between normal controls and tumor cells or tissues was ranging from 70% to 100%. The magnitude of increase of these miRNAs in pancreatic cancer samples was ranging from 3 to 2018 fold of normal controls. Pancreatic cancer tissues or cell lines have a unique miRNA profiling pattern at the individual basis as compared with relatively normal pancreatic tissues or cells as well as pancreatitis tissue. Upregulation of eight miRNAs occurs in the most of pancreatic cancer tissues and cell types. These miRNAs may share common pathways in pancreatic cancer pathogenesis. This study may provide useful information for further investigations of functional roles of miRNAs in pancreatic cancer development, progression, diagnosis and prognosis.
DOI: 10.1038/nature03702
发表时间: 2005-06-09
期刊: NATURE
影响因子: 64.8
作者:
Lu, J;Getz, G;Golub, TR
通讯作者: Golub, TR
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影响因子: 254.7
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