Long intergenic noncoding RNA 00673 promotes non-small-cell lung cancer metastasis by binding with EZH2 and causing epigenetic silencing of HOXA5.
Long intergenic noncoding RNA 00673 promotes non-small-cell lung cancer metastasis by binding with EZH2 and causing epigenetic silencing of HOXA5.
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长基因间非编码RNA 00673通过与EZH2结合并引起HOXA5表观遗传沉默促进非小细胞肺癌转移
DOI：
10.18632/oncotarget.16158
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发表时间：
2017-05-16
期刊：
影响因子：
--
通讯作者：
Song Y
中科院分区：
文献类型：
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作者：
Ma C;Wu G;Zhu Q;Liu H;Yao Y;Yuan D;Liu Y;Lv T;Song Y
癌细胞的转移是癌症治疗的有利结果的关键障碍。最近发现了长链非编码RNA在包括转移在内的多种生物学过程中的功能作用。在我们以前的工作中，我们报道了linc 00673在NSCLC组织中的表达增加与肿瘤大小、淋巴结转移、TNM分期以及NSCLC细胞增殖增加呈正相关，无论是在体外还是在体内。在这项研究中，我们证明了linc 00673的异位表达促进了NSCLC细胞的迁移和侵袭。此外，我们的结果表明linc 00673可以通过在其启动子区域招募表观遗传抑制子EZH 2来沉默HOXA 5的表达。HOXA 5是一种抑癌基因，通过调节细胞骨架重塑抑制NSCLC细胞的转移。综上所述，我们首次鉴定了lin00673在促进NSCLC细胞侵袭和迁移中的作用。这项研究的见解可能有助于确定NSCLC的新治疗靶点。
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.