Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba, Japan.
Genomics. 2010 Apr;95(4):210-6. doi: 10.1016/j.ygeno.2010.02.002. Epub 2010 Feb 11.
Malignant mesothelioma is a highly aggressive tumor arising from serosal surfaces of the pleura and is triggered by past exposure to asbestos. Currently, there is no widely accepted treatment for mesothelioma. Development of effective drug treatments for human cancers requires identification of therapeutic molecular targets. We therefore conducted a large-scale functional screening of mesothelioma cells using a genome-wide small interfering RNA library. We determined that knockdown of 39 genes suppressed mesothelioma cell proliferation. At least seven of the 39 genes-COPA, COPB2, EIF3D, POLR2A, PSMA6, RBM8A, and RPL18A-would be involved in anti-apoptotic function. In particular, the COPA protein was highly expressed in some mesothelioma cell lines but not in a pleural mesothelial cell line. COPA knockdown induced apoptosis and suppressed tumor growth in a mesothelioma mouse model. Therefore, COPA may have the potential of a therapeutic target and a new diagnostic marker of mesothelioma.
恶性间皮瘤是一种源自胸膜浆膜表面的高度侵袭性肿瘤，由过去接触石棉引起。目前，间皮瘤尚无广泛接受的治疗方法。开发针对人类癌症的有效药物治疗方法需要确定治疗性分子靶标。因此，我们使用全基因组小干扰 RNA 文库对间皮瘤细胞进行了大规模功能筛选。我们确定敲低 39 个基因可抑制间皮瘤细胞增殖。在这 39 个基因中，至少有 7 个基因（COPA、COPB2、EIF3D、POLR2A、PSMA6、RBM8A 和 RPL18A）参与抗细胞凋亡功能。特别是 COPA 蛋白在一些间皮瘤细胞系中高度表达，但在胸膜间皮细胞系中不表达。COPA 敲低可诱导间皮瘤小鼠模型中的细胞凋亡并抑制肿瘤生长。因此，COPA 可能具有作为治疗靶标的潜力和间皮瘤的新诊断标志物。
