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lncRNA DRHC inhibits proliferation and invasion in hepatocellular carcinoma via c-Myb-regulated MEK/ERK signaling.

Runzhou ZhuangXuanyu ZhangDi LuJianguo WangJianyong ZhuoXuyong WeiQi LingHaiyang XieShushen ZhenXiao Xu
Published in: Molecular carcinogenesis (2018)
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.
Keyphrases
  • long non coding rna
  • signaling pathway
  • pi k akt
  • poor prognosis
  • epithelial mesenchymal transition
  • long noncoding rna
  • transcription factor
  • cell proliferation
  • oxidative stress
  • circulating tumor cells