Long non-coding RNA Myd88 promotes growth and metastasis in hepatocellular carcinoma via regulating Myd88 expression through H3K27 modification

Cell Death Dis. 2017 Oct 12;8(10):e3124. doi: 10.1038/cddis.2017.519.

Abstract

Enhanced Myd88 expression has been found in various parenchymal tumors especially in hepatocellular carcinoma with little mechanism of its upregulation known. A lot of long non-coding RNAs are reported to regulate the protein-coding genes which have location association through various mechanisms. In our study we confirmed a new long non-coding RNA Myd88 aberrant upregulated in HCC located upstream of Myd88 and verified a positive regulation relationship between them indicating that Lnc-Myd88 might participate in the enhanced expression of Myd88 in HCC. The gain- and loss-of-function analysis revealed that Lnc-Myd88 could promote the proliferation and metastasis of HCC both in vitro and in vivo. In addition, ChIP assays demonstrated that Lnc-Myd88 might increase Myd88 expression through enhancing H3K27Ac in the promoter of Myd88 gene, thus resulting in the activation of both NF-κB and PI3K/AKT signal pathways. In conclusion, we proposed that Lnc-Myd88 might serve as a novel diagnosis and therapeutic target for HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic / genetics*
  • Hep G2 Cells
  • Histones / metabolism
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Myeloid Differentiation Factor 88 / genetics*
  • NF-kappa B / genetics
  • Neoplasm Invasiveness / genetics
  • Neoplasm Transplantation
  • Phosphatidylinositol 3-Kinases / metabolism
  • Promoter Regions, Genetic / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA Interference
  • RNA, Long Noncoding / genetics*
  • RNA, Small Interfering / genetics
  • Transplantation, Heterologous

Substances

  • Histones
  • MYD88 protein, human
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt