Ma Chenhui, Wu Guannan, Zhu Qingqing, Liu Hongbing, Yao Yanwen, Yuan Dongmei, Liu Yafang, Lv Tangfeng, Song Yong
Department of Respiratory Medicine, Jinling Hospital, Nanjing 210002, China.
Nanjing University Institute of Respiratory Medicine, Nanjing 210002, China.
Oncotarget. 2017 May 16;8(20):32696-32705. doi: 10.18632/oncotarget.16158.
Metastasis of cancer cells is a key impediment to favorable outcomes of cancer treatment. Functional roles of long noncoding RNAs in several biological processes, including metastasis, have recently been discovered. In our previous work, we reported a positive correlation of increased expression of linc00673 in NSCLC tissues with tumor size, lymph node metastasis, TNM stage, and increased proliferation of NSCLC cells, both, in vitro and in vivo. In this study, we demonstrate that ectopic expression of linc00673 promotes migration and invasion of NSCLC cells. Furthermore, our results indicate that linc00673 could silence HOXA5 expression by recruiting epigenetic repressor, EZH2, at its promoter regions. HOXA5 was identified as a tumor suppressor gene, which inhibited NSCLC cell metastasis by regulating cytoskeletal remodeling. To summarize, we for the first time identified the role of lin00673 in promoting invasion and migration of NSCLC cells. Insights from this study may help to identify novel therapeutic targets for NSCLC.
癌细胞转移是癌症治疗取得良好疗效的关键障碍。长链非编码RNA在包括转移在内的多个生物学过程中的功能作用最近已被发现。在我们之前的工作中，我们报道了NSCLC组织中linc00673表达增加与肿瘤大小、淋巴结转移、TNM分期以及NSCLC细胞在体外和体内增殖增加呈正相关。在本研究中，我们证明linc00673的异位表达促进NSCLC细胞的迁移和侵袭。此外，我们的结果表明linc00673可以通过在其启动子区域募集表观遗传抑制因子EZH2来沉默HOXA5的表达。HOXA5被鉴定为一种肿瘤抑制基因，它通过调节细胞骨架重塑来抑制NSCLC细胞转移。总之，我们首次确定了lin00673在促进NSCLC细胞侵袭和迁移中的作用。本研究的见解可能有助于识别NSCLC的新型治疗靶点。
