Tang Yi, Xiao GaoMing, Chen YueJun, Deng Yu
1st Department of Thoracic Surgery.
Department of Thoracic Radiation, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People's Republic of China.
Anticancer Drugs. 2018 Sep;29(8):725-735. doi: 10.1097/CAD.0000000000000650.
Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) functions as a crucial regulator of metastasis in lung cancer. The aim of this study is to unravel the underlying mechanisms of lncRNA MALAT1 in non-small-cell lung cancer (NSCLC). A cohort of 36 NSCLC tumor tissues and adjacent normal tissues was collected postoperatively from patients with NSCLC. qRT-PCR was performed to detect the expression of MALAT1 in both NSCLC tissues and cell lines. Cell migration and invasion were monitored by wound healing assay and transwell invasion assay. Western blot was used to detect the expression levels of epithelial-mesenchymal transition proteins and Akt/mTOR key components after treatment. Dual luciferase reporter assay coupled with qRT-PCR was used to verify the direct interaction between MALAT1 and miR-206. MALAT1 was significantly up-regulated in both NSCLC tissues and cell lines. High expression of MALAT1 correlated positively with tumor size and lymphatic metastasis in NSCLC, whereas no correlation was found between MALAT1 expression and sex, age, clinical stage, and histological grade. We also showed that MALAT1 promoted epithelial-mesenchymal transition, cell migration, and invasion by activating Akt/mTOR signaling in A549 and H1299 cells. miR-206 was a direct downstream target of MALAT1 in NSCLC. MALAT1 promoted cell migration and invasion by sponging miR-206 in NSCLC cells. In addition, miR-206 inhibited MALAT1-mediated activation of Akt/mTOR signaling in A549 and H1299 cells. lncRNA MALAT1 promotes migration and invasion of NSCLC by targeting miR-206 and activating Akt/mTOR signaling.
长链非编码RNA（lncRNA）转移相关肺腺癌转录本1（MALAT1）在肺癌转移中发挥关键调节作用。本研究旨在揭示lncRNA MALAT1在非小细胞肺癌（NSCLC）中的潜在机制。术后收集了36例NSCLC患者的肿瘤组织及癌旁正常组织。采用qRT-PCR检测NSCLC组织和细胞系中MALAT1的表达。通过伤口愈合试验和Transwell侵袭试验监测细胞迁移和侵袭。采用蛋白质免疫印迹法检测处理后上皮-间质转化蛋白和Akt/mTOR关键成分的表达水平。采用双荧光素酶报告基因检测结合qRT-PCR验证MALAT1与miR-206之间的直接相互作用。MALAT1在NSCLC组织和细胞系中均显著上调。MALAT1高表达与NSCLC的肿瘤大小和淋巴结转移呈正相关，而MALAT1表达与性别、年龄、临床分期和组织学分级之间未发现相关性。我们还发现，MALAT1通过激活A549和H1299细胞中的Akt/mTOR信号促进上皮-间质转化、细胞迁移和侵袭。miR-206是NSCLC中MALAT1的直接下游靶点。MALAT1通过在NSCLC细胞中海绵化miR-206促进细胞迁移和侵袭。此外，miR-206抑制A549和H1299细胞中MALAT1介导的Akt/mTOR信号激活。lncRNA MALAT1通过靶向miR-206并激活Akt/mTOR信号促进NSCLC的迁移和侵袭。
