Tumor invasion and metastasis regulated by microRNA-184 and microRNA-574-5p in small-cell lung cancer
Tumor invasion and metastasis regulated by microRNA-184 and microRNA-574-5p in small-cell lung cancer
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microRNA-184和microRNA-574-5p调控小细胞肺癌的肿瘤侵袭和转移
DOI：
10.18632/oncotarget.6338
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发表时间：
2015-12-29
期刊：
影响因子：
--
通讯作者：
Wu, Gang
中科院分区：
文献类型：
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作者：
Zhou, Rui;Zhou, Xiaoshu;Wu, Gang
小细胞肺癌（SCLC）是一种高度侵袭性的神经内分泌肿瘤，临床预后极差。转移是SCLC进展的关键事件，但其机制尚未完全阐明。 MicroRNA (miRNA) 已被证明参与癌症过程，但它们在 SCLC 中的功能也尚未得到深入研究。在这里，我们进行了微阵列和定量实时 PCR (qRT-PCR) 分析，以确定与 SCLC 转移和预后相关的 miRNA 以及血清和组织之间的相关性。我们还通过 3'UTR 报告基因检测和免疫印迹探索了这些 miRNA 有前途的分子机制。我们发现 miR-184 显着减弱 SCLC 的转移，而 miR-574-5p 则增强它。发现这两种 miRNA 通过抑制 U 型蛋白酪氨酸磷酸酶受体 (PTPRU) 或内皮 PAS 结构域蛋白 1 (EPAS1) 参与 β-连环蛋白信号传导。此外，miR-574-5p 被证实是 SCLC 的独立预后危险因素。总而言之，我们的研究结果对 SCLC 中的 miRNA 表达模式进行了全面分析，并表明 miRNA 可以作为 SCLC 的潜在治疗和预后预测因子。
Small-cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor that has an extremely poor clinical prognosis. Metastasis is the key event in SCLC progression, but its mechanism has not been fully elucidated. MicroRNAs (miRNAs) have been proven to participate in cancer processes, but their function in SCLC has not been thoroughly studied either. Here, we performed microarray and quantitative real-time PCR (qRT-PCR) analyses to identify the miRNAs associated with metastasis and prognosis in SCLC as well as the correlation between serum and tissue. We also explored these miRNAs' promising molecular mechanisms by 3'UTR reporter assay and immunoblotting. We showed thatmiR-184 significantly attenuated the metastasis of SCLC, whereas miR-574-5p enhanced it. Both miRNAs were found to participate in beta-catenin signaling by suppressing protein tyrosine phosphatase receptor type U (PTPRU) orendothelial PAS domain protein 1 (EPAS1). Furthermore, miR-574-5p was verified as an independent prognostic risk factor for SCLC. Taken together, our findings providea comprehensive analysis of the miRNA expression pattern in SCLC and indicate that miRNAs may serve as potential therapeutic and prognostic predictors in SCLC.