lncRNA DRHC inhibits proliferation and invasion in hepatocellular carcinoma via c-Myb-regulated MEK/ERK signaling
lncRNA DRHC inhibits proliferation and invasion in hepatocellular carcinoma via c-Myb-regulated MEK/ERK signaling
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lncRNA DRHC 通过 c-Myb 调节的 MEK/ERK 信号传导抑制肝细胞癌的增殖和侵袭
DOI：
10.1002/mc.22934
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发表时间：
2018
影响因子：
4.6
通讯作者：
Xiao Xu
中科院分区：
文献类型：
--
作者：
Runzhou Zhuang;Xuanyu Zhang;Di Lu;Jianguo Wang;Jianyong Zhuo;Xuyong Wei;Qi Ling;Haiyang Xie;Shusen Zheng;Xiao Xu
越来越多的证据表明，长链非编码RNA（lncRNA）在肝细胞癌（HCC）中起着至关重要的作用。在这里，我们报道了一种新的lncRNA，CTC-505 O3（lncRNA DRHC），它在HCC中下调，其低表达与生存率低下相关。功能获得研究表明，它在体外抑制HCC细胞系的增殖、迁移、侵袭和上皮间质转化（EMT）。lncRNA DRHC还抑制体内致瘤性。在机制实验中，基于NGS的GO分析表明MAPK信号转导受到的影响最大。结果通过Western blot证实，并且这种作用被MEK 1/2特异性抑制剂Trametinib或ERK 1/2抑制剂SCH 772984消除。此外，曲美替尼消除了增殖和侵袭的差异。此外，我们发现lncRNA DRHC与MYBBP 1A相互作用并通过c-Myb调节MEK/ERK信号传导。综上所述，我们的研究结果表明lncRNA DRHC在HCC进展中起关键作用，并可能作为一种新的治疗靶点。
Accumulating evidence indicates that long non‐coding RNAs (lncRNAs) play a crucial role in hepatocellular carcinoma (HCC). Here, we reported a novel lncRNA, CTC‐505O3 (lncRNA DRHC), that was downregulated in HCC and its low expression was associated with dismal survival. Gain‐of‐function studies indicated that it inhibited proliferation, migration, invasion, and epithelial‐mesenchymal transition (EMT) in HCC cell lines in vitro. lncRNA DRHC also inhibited tumorigenicity in vivo. In mechanistic experiments, GO analysis based on NGS indicated that MAPK signaling was most affected. The result was confirmed by Western blot and this effect was abolished either by MEK1/2 specific inhibitor Trametinib or ERK1/2 inhibitor SCH772984. In addition, differences in proliferation and invasion were abrogated by Trametinib. Moreover, we found that lncRNA DRHC interacted with MYBBP1A and modulated MEK/ERK signaling via c‐Myb. Taken together, our findings indicate that the lncRNA DRHC play a key role in HCC progression and may serve as a novel therapeutic target.