P2X7 mRNA expression in non-small cell lung cancer: MicroRNA regulation and prognostic value.

P2X7 mRNA expression in non-small cell lung cancer: MicroRNA regulation and prognostic value.
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DOI:
10.3892/ol.2014.2620
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发表时间:
2015-01
期刊:
影响因子:
2.9
通讯作者:
Fontanini G
Fontanini G
中科院分区:
医学4区
文献类型:
--
作者:
Boldrini L;Giordano M;Alì G;Melfi F;Romano G;Lucchi M;Fontanini G

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人类 P2X7 受体很重要,并且在肿瘤形成中表现出多种功能。目前,人们对其监管知之甚少。 P2X7 表达可能在转录后受到调节,并且推定的 microRNA (miRNA) 结合位点被认为参与其中。本研究的目的是确定 miRNA(miR-21、let-7 g 和 miR-205)是否调节 P2X7 mRNA 稳定性。此外,还研究了 P2X7 表达对非小细胞肺癌 (NSCLC) 患者的影响。使用定量逆转录聚合酶链反应对 96 例 NSCLC 病例中的 P2X7 mRNA 和成熟 Let-7g、miR-21 和 miR-205 表达水平进行定量。在所有样本中,还进行了表皮生长因子受体和 K-Ras 突变分析。与 P2X7 高表达的样品相比,P2X7 低表达的样品在 miR-21 表达方面表现出更高的倍数变化。与 K-Ras 野生型肿瘤患者相比,K-Ras 突变 NSCLC 患者的肿瘤中 miR-21 表达显着升高(P=0.003)。此外,为了评估 NSCLC 患者中 P2X7 表达与预后之间的关联,使用 Kaplan-Meier 方法进行生存分析。 P2X7 高表达的 NSCLC 患者与低表达的患者相比,无进展生存期和总生存期存在显着差异(分别为 P=0.03 和 P=0.02)。因此,我们假设携带 K-Ras 突变的 NSCLC 患者中 miR-21 的高水平表达可能受到复杂回路的调节,包括 P2X7 下调,这些过程共同可能促进肿瘤进展。
The human P2X7 receptor is significant and exhibits several functions in neoplasia. At present, little is known with regard to its regulation. P2X7 expression may be regulated post-transcriptionally and putative microRNA (miRNA) binding sites are considered to be involved. The aim of this study was to determine whether miRNAs (miR-21, let-7 g and miR-205) regulate P2X7 mRNA stability. In addition, the impact of P2X7 expression in patients with non-small cell lung cancer (NSCLC) was investigated. P2X7 mRNA and mature Let-7 g, miR-21, and miR-205 expression levels were quantified in 96 NSCLC cases using quantitative reverse transcription polymerase chain reaction. In all samples, epidermal growth factor receptor and K-Ras mutational analysis was also performed. Samples with low P2X7 expression were found to exhibit a higher fold change in miR-21 expression when compared with samples exhibiting high P2X7 expression. Significantly higher miR-21 expression was observed in the tumors of NSCLC patients with a K-Ras mutation when compared with patients who had K-Ras wild-type tumors (P=0.003). Additionally, to evaluate the association between P2X7 expression and prognosis in NSCLC patients, survival analysis was performed using the Kaplan-Meier method. A significant difference in the progression-free survival and overall survival in the NSCLC patients with high P2X7 expression was identified, when compared with that of patients with low expression (P=0.03 and P=0.02, respetively). Therefore, we hypothesized that high levels of miR-21 expression in NSCLC patients with K-Ras mutations may be regulated by a complex circuit, including P2X7 downregulation and together these processes may promote tumor progression.
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