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miR-372 表达的人肺腺癌细胞(CL 1-0)的比较蛋白质组学分析

Comparative proteomic profiling of human lung adenocarcinoma cells (CL 1-0) expressing miR-372.

机构信息

Institute of Molecular Biology, National Chung Hsing University, Taichung, Taiwan.

出版信息

Electrophoresis. 2012 Feb;33(4):675-88. doi: 10.1002/elps.201100329.

DOI:10.1002/elps.201100329
PMID:22451061
Abstract

Lung cancer is a common malignancy and has a poor overall prognosis. Widespread metastasis is a common phenomenon in non-small cell lung cancer (NSCLC). It has been demonstrated that cancer relapse and survival can be predicted by the presence of a five-microRNA (miRNA) signature independent of stage or histologic type in NSCLC patients. Among the five miRNAs in the signature, miR-372 has been shown to play a significant role in metastasis and in the development of human testicular germ cell tumors. In addition, there is evidence that miR-372 posttranscriptionally downregulates large tumor suppressor, homolog 2 (Lats2), resulting in tumorigenesis and proliferation. To further investigate the cellular mechanisms involved in miR-372-induced silencing, we conducted a comparative proteomic analysis of NSCLC CL 1-0 cells expressing miRNA-372 and/or vector only by using two-dimensional gel electrophoresis (2DE), two-dimensional difference gel electrophoresis (2D-DIGE), and LC/MS/MS. Proteins identified as being up- or downregulated were further classified according to their biological functions. Many of the proteins identified in our study may be potential diagnostic biomarkers of NSCLC, particularly phosphorylated eIF4A-I.

摘要

肺癌是一种常见的恶性肿瘤,整体预后较差。非小细胞肺癌(NSCLC)常发生广泛转移。已有研究表明,NSCLC 患者中存在由五个 microRNA(miRNA)组成的 miRNA 特征签名,该签名可独立于分期或组织学类型预测癌症复发和生存。在该特征签名的五个 miRNA 中,miR-372 已被证明在转移和人类睾丸生殖细胞肿瘤的发生发展中发挥重要作用。此外,有证据表明 miR-372 通过转录后下调大肿瘤抑制因子同源物 2(Lats2),导致肿瘤发生和增殖。为了进一步研究 miR-372 诱导沉默所涉及的细胞机制,我们通过二维凝胶电泳(2DE)、二维差异凝胶电泳(2D-DIGE)和 LC/MS/MS 对表达 miRNA-372 和/或载体的 NSCLC CL 1-0 细胞进行了比较蛋白质组学分析。根据其生物学功能对被鉴定为上调或下调的蛋白质进行了进一步分类。我们的研究中鉴定出的许多蛋白质可能是 NSCLC 的潜在诊断生物标志物,特别是磷酸化 eIF4A-I。

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