Department of Respiratory Medicine , Affiliated Hongqi Hospital of Mudanjiang Medical University , Mudanjiang 157011 , Heilongjiang , P. R. China.
Department of Ultrasound , Mudanjiang Women and Children's Hospital , Mudanjiang 157000 , Heilongjiang , P. R. China.
Mol Pharm. 2018 Apr 2;15(4):1682-1689. doi: 10.1021/acs.molpharmaceut.8b00071. Epub 2018 Mar 16.
Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer. MicroRNAs have been increasingly implicated in NSCLC and may serve as novel therapeutic targets to combat cancer. Here we investigated the functional implication of miR-188 in NSCLC. We first analyzed miR-188 expression in both NSCLC clinical samples and cancer cell lines. Next we investigated its role in A549 and H2126 cells with cell proliferation, migration, and apoptosis assays. To extend the in vitro study, we employed both xenograft model and LSL- K-ras G12D lung cancer model to examine the role of miR-188 in tumorigenesis. Last we tested MAP3K3 as miR-188 target in NSCLC model. MiR-188 expression was significantly downregulated at the NSCLC tumor sites and lung cancer cells. In vitro transfection of miR-188 reduced cell proliferation and migration potential and promoted cell apoptosis. In xenograft model, miR-188 inhibited tumor growth derived from cancer cells. Intranasal miR-188 administration reduced tumor formation in NSCLC animal model. MAP3K3 was validated as direct target of miR-188. Knocking down MAP3K3 in mice also inhibited tumorigenesis in LSL- K-ras G12D model. Our results demonstrate that miR-188 and its downstream target MAP3K3 could be a potential therapeutic target for NSCLC.
非小细胞肺癌（NSCLC）是最常见的肺癌类型。越来越多的证据表明 microRNAs 与 NSCLC 有关，并可能成为治疗癌症的新靶点。在这里，我们研究了 miR-188 在 NSCLC 中的功能意义。我们首先分析了 NSCLC 临床样本和癌细胞系中 miR-188 的表达。接下来，我们通过细胞增殖、迁移和凋亡实验研究了它在 A549 和 H2126 细胞中的作用。为了扩展体外研究，我们使用异种移植模型和 LSL-K-ras G12D 肺癌模型来研究 miR-188 在肿瘤发生中的作用。最后，我们在 NSCLC 模型中测试了 MAP3K3 作为 miR-188 的靶标。miR-188 在 NSCLC 肿瘤部位和肺癌细胞中的表达明显下调。miR-188 的体外转染降低了细胞的增殖和迁移能力，并促进了细胞凋亡。在异种移植模型中，miR-188 抑制了源自癌细胞的肿瘤生长。鼻内 miR-188 给药减少了 NSCLC 动物模型中的肿瘤形成。MAP3K3 被验证为 miR-188 的直接靶标。在小鼠中敲低 MAP3K3 也抑制了 LSL-K-ras G12D 模型中的肿瘤发生。我们的结果表明，miR-188 和其下游靶标 MAP3K3 可能是 NSCLC 的潜在治疗靶点。
