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整联蛋白通过 microRNA-218 靶向作用预测非小细胞肺癌的生存和复发。

Paxillin predicts survival and relapse in non-small cell lung cancer by microRNA-218 targeting.

机构信息

Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, ROC.

出版信息

Cancer Res. 2010 Dec 15;70(24):10392-401. doi: 10.1158/0008-5472.CAN-10-2341.

Abstract

Paxillin (PXN) gene mutations are associated with lung adenocarcinoma progression and PXN is known to be a target gene of microRNA-218 (miR-218). On this basis, we hypothesized that PXN overexpression via miR-218 suppression may promote tumor progression and metastasis and that PXN may predict survival and relapse in non-small cell lung cancer (NSCLC). Expression of miR-218 and PXN in 124 surgically resected lung tumors were evaluated by real-time PCR and immunohistochemical analysis. The prognostic value of miR-218 and PXN expression on overall survival (OS) and relapse-free survival (RFS) was analyzed by the Kaplan-Meier test and Cox regression analysis. miR-218 expression in lung tumors was negatively associated with PXN expression. Multivariate analyses showed that PXN and miR-218 might independently predict OS and RFS, respectively, in NSCLC. Moreover, patients with low miR-218 combined with PXN-positive had the worst OS and RFS among the 4 combinations. In a cell model, PXN was negatively regulated by miR-218 and cell proliferation, invasion, and soft agar colony formation were enhanced by PXN overexpression induced by miR-218 suppression. Taken together, our findings suggest that PXN overexpression induced by miR-218 suppression is an independent predictor of survival and relapse in NSCLC, highlighting PXN as a potential therapeutic target to improve clinical outcomes in this disease.

摘要

桩蛋白(PXN)基因突变与肺腺癌的进展相关,并且 PXN 已知是 microRNA-218(miR-218)的靶基因。在此基础上,我们假设通过抑制 miR-218 过表达 PXN 可能促进肿瘤的进展和转移,并且 PXN 可能预测非小细胞肺癌(NSCLC)的生存和复发。通过实时 PCR 和免疫组织化学分析评估了 124 例手术切除的肺肿瘤中 miR-218 和 PXN 的表达。通过 Kaplan-Meier 检验和 Cox 回归分析分析了 miR-218 和 PXN 表达对总生存(OS)和无复发生存(RFS)的预后价值。肺肿瘤中 miR-218 的表达与 PXN 的表达呈负相关。多变量分析表明,PXN 和 miR-218 可能分别独立预测 NSCLC 的 OS 和 RFS。此外,在 4 种组合中,miR-218 低结合 PXN 阳性的患者 OS 和 RFS 最差。在细胞模型中,miR-218 负调控 PXN,并且通过抑制 miR-218 诱导的 PXN 过表达增强了细胞增殖、侵袭和软琼脂集落形成。总之,我们的研究结果表明,miR-218 抑制诱导的 PXN 过表达是非小细胞肺癌生存和复发的独立预测因子,突出了 PXN 作为改善该疾病临床结局的潜在治疗靶点。

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