Zhang Rui, Xia Yuhong, Wang Zhixin, Zheng Jie, Chen Yafei, Li Xiaoli, Wang Yu, Ming Huaikun
Respiratory Diseases Ward 2, The Central Hospital of Xinxiang City, Xinxiang, China.
Respiratory Diseases Ward 2, The Central Hospital of Xinxiang City, Xinxiang, China.
Biochem Biophys Res Commun. 2017 Aug 19;490(2):406-414. doi: 10.1016/j.bbrc.2017.06.055. Epub 2017 Jun 13.
Circulating lncRNAs have been defined as a novel biomarker for non-small cell lung cancer (NSCLC), MALAT-1 was first identified lncRNA that was related to lung cancer metastasis. However, the relationship between exosomal lncRNAs and the diagnosis and prognosis of NSCLC was poorly understood. The aim of this study is to evaluate the clinical significance of serum exosomal MALAT-1 as a biomarker in the metastasis of NSCLC. In this study, we firstly isolated the exosomes from healthy subjects and NSCLC patients. Then we measured the expression levels of MALAT-1 contained in exosomes, and found that exosomal MALAT-1 was highly expressed in NSCLC patients, more importantly, the levels of exosomal MALAT-1 were positively associated with tumor stage and lymphatic metastasis. In addition, we decreased MALAT-1 expression by short hairpin RNA and conducted a series of assays including MTT, cell cycle, colony formation, wound-healing scratch and Annexin/V PI by flow cytometry in human lung cancer cell lines. These in vitro studies demonstrated that serum exosome-derived long noncoding RNA MALAT-1 promoted the tumor growth and migration, and prevented tumor cells from apoptosis in lung cancer cell lines. Taken together, this study shed a light on utilizing MALAT-1 in exosomes as a non-invasive serum-based tumor biomarker for diagnosis and prognosis of NSCLC.
循环长链非编码RNA（lncRNAs）已被定义为非小细胞肺癌（NSCLC）的一种新型生物标志物，MALAT-1是首个被鉴定出与肺癌转移相关的lncRNA。然而，外泌体长链非编码RNA与NSCLC的诊断及预后之间的关系却鲜为人知。本研究旨在评估血清外泌体MALAT-1作为NSCLC转移生物标志物的临床意义。在本研究中，我们首先从健康受试者和NSCLC患者中分离出了外泌体。然后我们检测了外泌体中所含MALAT-1的表达水平，发现外泌体MALAT-1在NSCLC患者中高表达，更重要的是，外泌体MALAT-1的水平与肿瘤分期及淋巴转移呈正相关。此外，我们通过短发夹RNA降低了MALAT-1的表达，并在人肺癌细胞系中进行了一系列实验，包括MTT、细胞周期、集落形成、伤口愈合划痕实验以及流式细胞术检测膜联蛋白V/碘化丙啶。这些体外研究表明，血清外泌体来源的长链非编码RNA MALAT-1促进了肺癌细胞系中的肿瘤生长和迁移，并抑制肿瘤细胞凋亡。综上所述，本研究为将外泌体中的MALAT-1用作NSCLC诊断和预后的非侵入性血清肿瘤生物标志物提供了依据。
