Department of Spinal Surgery, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China.
Department of Respiratory, The Fifth People's Hospital of Shanghai, Fudan university, Shanghai, China.
J Cell Physiol. 2018 Sep;233(9):6679-6688. doi: 10.1002/jcp.26325. Epub 2018 Apr 11.
lncRNAs can exert many biological effects in several cancer types. MALAT1 is a kind of lncRNA which is greatly overexpressed in several tumors including non-small cell lung cancer (NSCLC). However, the mechanism of MALAT1 in NSCLC still remains unclear. In our current study, we concentrated on the biological mechanism of MALAT1 in NSCLC. It was observed that MALAT1 was significantly upregulated in five human NSCLC cells including A549, H23, H522, H1299, and H460 cells compared to normal bronchial epithelial cell line 16HBE cells. On the contrary, miR-124 was remarkably downregulated, which indicated a potential negative correlation between miR-124 and MALAT1. MALAT1 inhibition can increase miR-124 expression in A549 and H460 cells. In addition, miR-124 mimics were able to repress MALAT1 expression and miR124 inhibitors can promote MALAT1 levels. Then it was found that shMALAT1 can inhibit NSCLC cell proliferation, colony formation and apoptosis, which can be reversed by miR-124 inhibitors. Bioinformatic analysis predicted the correlation between miR-124 and MALAT1. In addition, STAT3 was found to be a novel mRNA target of miR-124. Downregulation of MALAT1 can inhibit NSCLC development by enhancing miR-124 and decreasing STAT3 expression. We speculated that MALAT1can act as a competing endogenous lncRNA (ceRNA) to modulate miR-124/STAT3 in NSCLC. Taken these together, we revealed that MALAT1/miR-124/STAT3 was involved in NSCLC development.
lncRNAs 在多种癌症类型中可以发挥许多生物学效应。MALAT1 是一种在包括非小细胞肺癌（NSCLC）在内的多种肿瘤中高度过表达的 lncRNA。然而，MALAT1 在 NSCLC 中的作用机制仍不清楚。在我们目前的研究中，我们集中研究了 MALAT1 在 NSCLC 中的生物学机制。结果观察到，与正常支气管上皮细胞系 16HBE 细胞相比，五种人 NSCLC 细胞（A549、H23、H522、H1299 和 H460 细胞）中 MALAT1 显著上调。相反，miR-124 显著下调，表明 miR-124 和 MALAT1 之间存在潜在的负相关。MALAT1 抑制可增加 A549 和 H460 细胞中 miR-124 的表达。此外，miR-124 模拟物能够抑制 MALAT1 的表达，而 miR124 抑制剂可以促进 MALAT1 水平。然后发现 shMALAT1 可以抑制 NSCLC 细胞增殖、集落形成和凋亡，而 miR-124 抑制剂可以逆转这一作用。生物信息学分析预测了 miR-124 和 MALAT1 之间的相关性。此外，发现 STAT3 是 miR-124 的一种新型 mRNA 靶标。下调 MALAT1 可以通过增强 miR-124 和降低 STAT3 表达来抑制 NSCLC 的发展。我们推测 MALAT1 可以作为竞争性内源 lncRNA（ceRNA）来调节 NSCLC 中的 miR-124/STAT3。综上所述，我们揭示了 MALAT1/miR-124/STAT3 参与 NSCLC 的发生发展。
