Shen Liqin, Chen Lei, Wang Yongsheng, Jiang Xiaochun, Xia Hongping, Zhuang Zhixiang
Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, China.
J Neurooncol. 2015 Jan;121(1):101-8. doi: 10.1007/s11060-014-1613-0. Epub 2014 Sep 14.
Brain metastasis often has a poor prognosis in patients with advanced non-small cell lung cancer (NSCLC). Therefore, it is urgent to identify factors associated with lung cancer brain metastasis. Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) also known as noncoding nuclear-enriched abundant transcript 2 is a long noncoding RNA, which is highly conserved amongst mammals. It has been shown to be increased in a variety of tumors including NSCLC and regulate the expression of metastasis-associated genes. However, the role of MALAT1 in lung cancer brain metastasis has not been investigated. In this study, we examined the level of MALAT1 in 78 cases of NSCLC samples with 19 brain metastasis and 59 non-brain metastasis by qRT-PCR. We observed that the level of MALAT1 was significantly higher in brain metastasis than that of non brain metastasis samples (P < 0.001). The level of MALAT1 was associated with patients' survival. To investigate the role of MALAT1 in brain metastasis, we established a highly invasive and metastatic cell subline using the brain metastasis lung cancer cell H1915. We found that MALAT1 is increased in highly invasive subline of brain metastasis lung cancer cells. Further functional studies indicate that silencing MALAT1 inhibits highly invasive subline of brain metastasis lung cancer cell migration and metastasis by inducing epithelial-mesenchymal transition (EMT). Therefore, increased level of long noncoding RNA MALAT1 promotes lung cancer brain metastasis by inducing EMT, which may be a promising prognosis factor and therapeutic target to treat lung cancer brain metastasis in future.
脑转移在晚期非小细胞肺癌（NSCLC）患者中通常预后较差。因此，迫切需要确定与肺癌脑转移相关的因素。转移相关肺腺癌转录本1（MALAT1），也称为非编码核富集丰富转录本2，是一种长链非编码RNA，在哺乳动物中高度保守。已证明它在包括NSCLC在内的多种肿瘤中表达增加，并调节转移相关基因的表达。然而，MALAT1在肺癌脑转移中的作用尚未得到研究。在本研究中，我们通过qRT-PCR检测了78例NSCLC样本（其中19例有脑转移，59例无脑转移）中MALAT1的水平。我们观察到，脑转移样本中MALAT1的水平显著高于无脑转移样本（P < 0.001）。MALAT1的水平与患者的生存率相关。为了研究MALAT1在脑转移中的作用，我们使用脑转移肺癌细胞H1915建立了一个高侵袭性和转移性的细胞亚系。我们发现MALAT1在脑转移肺癌细胞的高侵袭性亚系中表达增加。进一步的功能研究表明，沉默MALAT1可通过诱导上皮-间质转化（EMT）抑制脑转移肺癌细胞高侵袭性亚系的迁移和转移。因此，长链非编码RNA MALAT1水平的升高通过诱导EMT促进肺癌脑转移，这可能是未来治疗肺癌脑转移的一个有前景的预后因素和治疗靶点。
