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

Mol Carcinog. 2019 Mar;58(3):366-375. doi: 10.1002/mc.22934. Epub 2018 Nov 25.

Abstract

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.

Keywords: MEK/ERK; MYBBP1A; hepatocellular carcinoma; lncRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Proliferation*
  • DNA-Binding Proteins
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • MAP Kinase Kinase 1 / genetics
  • MAP Kinase Kinase 1 / metabolism
  • MAP Kinase Kinase 2 / genetics
  • MAP Kinase Kinase 2 / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Neoplasm Invasiveness
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nucleocytoplasmic Transport Proteins / genetics
  • Nucleocytoplasmic Transport Proteins / metabolism
  • Prognosis
  • Proto-Oncogene Proteins c-myb / genetics
  • Proto-Oncogene Proteins c-myb / metabolism*
  • RNA, Long Noncoding / genetics*
  • RNA-Binding Proteins
  • Signal Transduction
  • Survival Rate
  • Transcription Factors
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • MYB protein, human
  • MYBBP1A protein, human
  • Nuclear Proteins
  • Nucleocytoplasmic Transport Proteins
  • Proto-Oncogene Proteins c-myb
  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • Transcription Factors
  • MAP2K2 protein, human
  • MAPK1 protein, human
  • MAPK3 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • MAP Kinase Kinase 1
  • MAP Kinase Kinase 2
  • MAP2K1 protein, human