The long noncoding RNA, EGFR-AS1, a target of GHR, increases the expression of EGFR in hepatocellular carcinoma

Tumour Biol. 2016 Jan;37(1):1079-89. doi: 10.1007/s13277-015-3887-z. Epub 2015 Aug 14.

Abstract

LncRNA has provided an important new perspective regarding gene regulation. Both the expression and activation of EGFR have been proven to be under the tight control of the GHR pathway. EGFR-AS1 has been found to inhibit the expression of EGFR. GHR-siRNA and EGFR-AS1-siRNA were transfected into HCC cell lines, and a series of WB, q-PCR, and IF experiments was conducted to evaluate whether EGFR-AS1 participated in the regulation of GHR and EGFR. We found that impeded expression of GHR decreased the expression of EGFR and EGFR-AS1 in vivo and in vitro. Then, it was verified that EGFR and EGFR-AS1 were relatively upregulated in HCC tissue, and they were significantly related to some clinical characteristics and patient prognosis. Furthermore, EGFR-AS1 was determined to promote HCC development by improving the ability of invasion and proliferation of HCC cells in vitro, and it was also found to affect the cell cycle. Our study identified that EGFR-AS1 may promote HCC genesis and development. EGFR-AS1 may act as a prognostic factor in HCC. More importantly, we observed that the inhibition of EGFR-AS1 in HCC cells significantly impeded cell proliferation and invasion in vivo, which might provide a potential possibility for targeted therapy of HCC.

Keywords: EGFR-AS1; Epidermal growth factor receptor; Growth hormone receptor; Hepatocellular carcinoma; Long noncoding RNA.

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Carrier Proteins / genetics*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Models, Animal
  • Epithelial-Mesenchymal Transition
  • ErbB Receptors / genetics*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • Mice, Knockout
  • Neoplasm Metastasis
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • Tumor Burden
  • Up-Regulation

Substances

  • Carrier Proteins
  • RNA, Long Noncoding
  • ErbB Receptors
  • somatotropin-binding protein