Department of Endoscopic Diagnosis and Treatment Center, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Henan, China.
Medical Genetic Institute, Henan Provincial People's Hospital, Henan, China.
Life Sci. 2020 Aug 1;254:117238. doi: 10.1016/j.lfs.2019.117238. Epub 2019 Dec 28.
MicroRNA-27b (miR-27b) has been shown to play a role in the progression of many different forms of cancer, but its specific relevance in the context of non-small cell lung cancer (NSCLC) remains uncertain. As such, this study sought to explore the role of miR-27b in NSCLC and the mechanisms whereby it functions.
We quantified miR-27b and target gene expression via quantitative real-time PCR (RT-qPCR).We then used functional including proliferation assays, migration assay, flow cytometry, and western blotting to explore the mechanisms whereby miR-27b functions in vitro and in vivo. We additionally confirmed miR-27b target genes via luciferase reporter assay.
We observed a marked decrease in miR-27b expression in NSCLC patient samples relative to paracancerous control tissues. We further found that altering miR-27b expression levels in vitro affected NSCLC tumor cell migration, proliferation, and ability to undergo epithelial-mesenchymal transition. Through the use of target prediction algorithms we identified Snail to be a miR-27b target protein that was suppressed when this miRNA was highlight expressed. Lastly, we found miR-27b expression to increase NSCLC cell sensitivity to cisplatin through its ability to target Snail.
Our results clearly demonstrate that miR-27b can suppress NSCLC tumor development and progression, highlighting this miR-27b/Snail1 axis as putative target for the therapeutic treatment of NSCLC.
标题 目的：MicroRNA-27b（miR-27b）已被证明在多种不同形式的癌症进展中发挥作用，但在非小细胞肺癌（NSCLC）中的具体相关性尚不确定。因此，本研究旨在探讨 miR-27b 在 NSCLC 中的作用及其作用机制。
我们通过定量实时 PCR（RT-qPCR）定量测定 miR-27b 和靶基因的表达。然后，我们使用功能包括增殖测定、迁移测定、流式细胞术和 Western blot 来探讨 miR-27b 在体外和体内发挥作用的机制。我们还通过荧光素酶报告基因测定证实了 miR-27b 的靶基因。
我们观察到 NSCLC 患者样本中 miR-27b 的表达明显降低，与癌旁对照组织相比。我们进一步发现，体外改变 miR-27b 表达水平会影响 NSCLC 肿瘤细胞的迁移、增殖和上皮-间充质转化能力。通过使用靶标预测算法，我们确定 Snail 是 miR-27b 的靶标蛋白，当这种 miRNA 高表达时，该蛋白受到抑制。最后，我们发现 miR-27b 通过靶向 Snail 增加 NSCLC 细胞对顺铂的敏感性。
我们的研究结果清楚地表明，miR-27b 可以抑制 NSCLC 肿瘤的发生和发展，突出了 miR-27b/Snail1 轴作为 NSCLC 治疗的潜在靶标。
