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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >miR-200a, miR-200b and miR-429 Are Onco-miRs that Target the PTEN Gene in Endometrioid Endometrial Carcinoma
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miR-200a, miR-200b and miR-429 Are Onco-miRs that Target the PTEN Gene in Endometrioid Endometrial Carcinoma

机译:miR-200a,miR-200b和miR-429是靶向子宫内膜样子宫内膜癌PTEN基因的Onco-miRs。

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摘要

Endometrioid endometrial carcinoma (EEC) is a common malignancy of the female genital tract. However, no adequate biomarker is currently available for predicting the prognosis of this cancer. Recent studies have revealed dysregulated expression of several microRNAs (miRNAs) in various cancer tissues, and therefore, these cancer-associated miRNAs (also called onco-miRs) could be promising prognostic biomarkers of cancer progression or metastasis. In this study, in order to identify onco-miRs and their possible targets involved in EEC, we performed microarray-based integrative analyses of miRNA and mRNA expression in specimens excised from EEC lesions and adjacent normal endometrial tissues. Using integrated statistical analyses, we identified miR-200a, miR-200b and miR-429 as highly up-regulated onco-miRs in EECs. Conversely, we detected expression of a tumor-suppressor gene, phosphatase and tensin homolog (PTEN), which was predicted in silico using a miRNA-targeting mRNA prediction algorithm, as a target of the three miRNAs and which was down-regulated in EECs. Furthermore, these miRNAs were validated to target PTEN experimentally using luciferase assays and real-time polymerase chain reaction. These results suggest that the occurrence of EEC is, at least in part, mediated by miRNA-induced suppression of PTEN expression.
机译:子宫内膜样子宫内膜癌(EEC)是女性生殖道的常见恶性肿瘤。但是,目前没有足够的生物标志物可用于预测这种癌症的预后。最近的研究表明,在各种癌症组织中几种microRNA(miRNA)的表达失调,因此,这些与癌症相关的miRNA(也称为onco-miRs)有望成为癌症进展或转移的预后生物标志物。在这项研究中,为了鉴定onco-miRs及其可能参与EEC的靶标,我们对从EEC病变和邻近正常子宫内膜组织切除的标本中的miRNA和mRNA表达进行了基于微阵列的整合分析。使用综合的统计分析,我们确定了miR-200a,miR-200b和miR-429是EEC中高度上调的癌基因miR。相反,我们检测到肿瘤抑制基因,磷酸酶和张力蛋白同源物(PTEN)的表达,这是使用miRNA靶向mRNA预测算法在计算机上预测的,作为三种miRNA的靶标,并且在EEC中被下调。此外,使用荧光素酶测定法和实时聚合酶链反应,通过实验验证了这些miRNA靶向PTEN。这些结果表明,EEC的发生至少部分地由miRNA诱导的PTEN表达的抑制介导。

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