Department of Medical Laboratory, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China.
School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan 430065, China.
Oxid Med Cell Longev. 2019 Jun 18;2019:9719723. doi: 10.1155/2019/9719723. eCollection 2019.
Metastasis is the leading cause of high mortality in lung cancer patients, and metastatic lung cancer is difficult to treat. miRNAs are involved in various biological processes of cancer, including metastasis. Our previous studies revealed that miR-25 promoted non-small-cell lung cancer (NSCLC) cell proliferation and suppressed cell apoptosis by directly targeting and . In this work, we further explored the miR-25 expression in NSCLC patients in the Cancer Genome Atlas (TCGA) database and measured the miR-25 expression levels in the tissues of NSCLC patients and cell lines. miR-25 was overexpressed in both NSCLC tissues and cell lines. NSCLC patients who expressed a higher level of miR-25 exhibited worse overall survival than those with a lower level of miR-25. Overexpression of miR-25 enhanced NSCLC cell migration and invasion, while the inhibition of miR-25 exhibited the opposite effects. We identified the large tumor suppressor homology 2 () as a new target gene of miR-25 in lung cancer. The effects of miR-25 on promoting NSCLC cell migration and invasion were at least partially due to activation of the Hippo signaling pathway. Additionally, miR-25 antagomir inhibited xenograft tumor growth and metastasis by the upregulation of LATS2. Taken together, our findings demonstrate that miR-25 contribute to lung cancer cell proliferation and metastasis by targeting the LATS2/YAP signaling pathway, which implicate miR-25 as a promising therapeutic target for lung cancer metastasis. Given that oxidative stress induces the overexpression of miR-25 and plays a critical role in cancer progression, this study establishes miR-25 as an intermediate between oxidative stress and lung cancer metastasis.
转移是肺癌患者高死亡率的主要原因，转移性肺癌难以治疗。miRNAs 参与癌症的各种生物学过程，包括转移。我们之前的研究表明，miR-25 通过直接靶向 和 促进非小细胞肺癌（NSCLC）细胞增殖并抑制细胞凋亡。在这项工作中，我们进一步在癌症基因组图谱（TCGA）数据库中研究了 NSCLC 患者的 miR-25 表达，并测量了 NSCLC 患者组织和细胞系中的 miR-25 表达水平。miR-25 在 NSCLC 组织和细胞系中均过度表达。miR-25 表达水平较高的 NSCLC 患者的总生存期比 miR-25 表达水平较低的患者差。miR-25 的过表达增强了 NSCLC 细胞的迁移和侵袭，而 miR-25 的抑制则表现出相反的效果。我们确定了大肿瘤抑制因子同源物 2（）作为肺癌中 miR-25 的新靶基因。miR-25 通过激活 Hippo 信号通路对促进 NSCLC 细胞迁移和侵袭的作用至少部分是由于激活了 Hippo 信号通路。此外，miR-25 拮抗剂通过上调 LATS2 抑制异种移植肿瘤的生长和转移。总之，我们的研究结果表明，miR-25 通过靶向 LATS2/YAP 信号通路促进肺癌细胞增殖和转移，这表明 miR-25 可能是治疗肺癌转移的有前途的靶点。鉴于氧化应激诱导 miR-25 的过度表达并在癌症进展中发挥关键作用，本研究确立了 miR-25 作为氧化应激与肺癌转移之间的中间介质。
