Department of Surgery First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
NHFPC Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China.
Mol Carcinog. 2019 Mar;58(3):366-375. doi: 10.1002/mc.22934. Epub 2018 Nov 25.
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.
越来越多的证据表明，长非编码 RNA（lncRNA）在肝细胞癌（HCC）中发挥着关键作用。在这里，我们报道了一种新型的 lncRNA，CTC-505O3（lncRNA DRHC），它在 HCC 中表达下调，其低表达与预后不良相关。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-间充质转化（EMT）。lncRNA DRHC 也在体内抑制了肿瘤发生。在机制实验中，基于 NGS 的 GO 分析表明 MAPK 信号通路受到的影响最大。Western blot 结果证实了这一点，该效应被 MEK1/2 特异性抑制剂 Trametinib 或 ERK1/2 抑制剂 SCH772984 所消除。此外，Trametinib 消除了增殖和侵袭的差异。此外，我们发现 lncRNA DRHC 与 MYBBP1A 相互作用，并通过 c-Myb 调节 MEK/ERK 信号通路。总之，我们的研究结果表明，lncRNA DRHC 在 HCC 进展中发挥着关键作用，可能成为一种新的治疗靶点。
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