Elevated TFAP4 regulates lncRNA TRERNA1 to promote cell migration and invasion in gastric cancer
Elevated TFAP4 regulates lncRNA TRERNA1 to promote cell migration and invasion in gastric cancer
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TFAP4升高调节lncRNA TRERNA1促进胃癌细胞迁移和侵袭
DOI：
10.3892/or.2018.6466
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发表时间：
2018-08-01
期刊：
影响因子：
4.2
通讯作者：
Fan, Hong
中科院分区：
文献类型：
--
作者：
Wu, Huazhang;Liu, Xiufang;Fan, Hong
癌细胞的侵袭和转移是恶性肿瘤患者高死亡率的主要原因。越来越多的证据表明，长链非编码RNA（lncRNA）表达异常可能参与肿瘤的侵袭和转移。然而，lncRNA的异常表达的调节机制在很大程度上仍然未知，尽管lncRNA作为肿瘤抑制和致癌功能的驱动因素的作用近年来已经出现在流行的癌症类型中。在本研究中，我们确定了转录因子，激活增强子结合蛋白4（TFAP 4），作为翻译调节长非编码RNA 1（TRERNA 1），已被证明是促进胃癌（GC）细胞的侵袭和转移的关键调制器。我们发现TRERNA 1在胃癌发生过程中上调，并促进胃癌细胞的迁移和侵袭。通过生物信息学分析，我们发现在TRERNA 1的启动子区域存在几个TFAP 4的潜在结合位点。TFAP 4的敲低显著降低了胃癌细胞系中TRERNA 1的表达水平，而TFAP 4的异位表达显著增加了胃癌细胞系中TRERNA 1的表达水平。双荧光素酶报告基因检测结合染色质免疫沉淀（ChIP）显示TFAP 4通过与TRERNA 1启动子中的E-box基序结合特异性调节TRERNA 1的转录活性。此外，TFAP 4与TRERNA 1在胃癌组织中的表达水平呈正相关，提示TFAP 4可直接调控TRERNA 1的表达。在本研究中，我们提供了一个新的潜在的治疗GC的目标和策略。
Cancer cell invasion and metastasis are the leading causes of the high mortality rates in patients with malignant tumors. There is accumulating evidence to indicate that dysregulated long non-coding RNAs (lncRNAs) may be involved in the progression of tumor invasion and metastasis. However, the regulatory mechanisms of the aberrant expression of lncRNAs remain largely unknown, although the roles of lncRNAs as drivers of tumor suppressive and oncogenic functions have appeared in prevalent cancer types in recent years. In the present study, we identified that the transcription factor, activating enhancer-binding protein 4 (TFAP4), acts as a key modulator of translation regulatory long non-coding RNA 1(TRERNA1), which has been proven to promote the invasion and metastasis of gastric cancer (GC) cells. We revealed that TRERNA1 was upregulated in gastric carcinogenesis and promoted cell migration and invasion in GC. Using bioinformatics analysis, we observed that there were several potential binding sites of TFAP4 in the promoter region of TRERNA1. The knockdown of TFAP4 significantly reduced the expression level of TRERNA1, whereas the ectopic expression of TFAP4 significantly increased the expression level of TRERNA1 in GC cell lines. Dual luciferase reporter assay combined with chromatin immunoprecipitation (ChIP) revealed that TFAP4 specifically regulated the transcriptional activity of TRERNA1 by binding to the E-box motifs in the TRERNA1 promoter. In addition, there was a positive correlation between the TFAP4 and TRERNA1 expression level in clinical GC cases, which also indicated that TFAP4 can directly modulate the expression of TRERNA1. In the present study, we provide a novel potential therapeutic target and strategy for GC.