Role of long non-coding RNA HULC in cell proliferation, apoptosis and tumor metastasis of gastric cancer: a clinical and in vitro investigation

Oncol Rep. 2014 Jan;31(1):358-64. doi: 10.3892/or.2013.2850. Epub 2013 Nov 14.

Abstract

Long non-coding RNAs (lncRNAs) are emerging as key molecules in human cancer. Highly upregulated in liver cancer (HULC), an lncRNA, has recently been revealed to be involved in hepatocellular carcinoma development and progression. It remains unclear, however, whether HULC plays an oncogenic role in human gastric cancer (GC). In the present study, we demonstrated that HULC was significantly overexpressed in GC cell lines and GC tissues compared with normal controls, and this overexpression was correlated with lymph node metastasis, distant metastasis and advanced tumor node metastasis stages. In addition, a receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic values and the area under the ROC curve of HULC was up to 0.769. To uncover its functional importance, gain- and loss-of-function studies were performed to evaluate the effect of HULC on cell proliferation, apoptosis and invasion in vitro. Overexpression of HULC promoted proliferation and invasion and inhibited cell apoptosis in SGC7901 cells, while knockdown of HULC in SGC7901 cells showed the opposite effect. Mechanistically, we discovered that overexpression of HULC could induce patterns of autophagy in SGC7901 cells; more importantly, autophagy inhibition increased overexpression of HULC cell apoptosis. We also determined that silencing of HULC effectively reversed the epithelial-to-mesenchymal transition (EMT) phenotype. In summary, our results suggest that HULC may play an important role in the growth and tumorigenesis of human GC, which provides us with a new biomarker in GC and perhaps a potential target for GC prevention, diagnosis and therapeutic treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apoptosis / genetics*
  • Autophagy / genetics*
  • Biomarkers, Tumor / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Lymphatic Metastasis / genetics
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Metastasis
  • RNA, Long Noncoding / biosynthesis
  • RNA, Long Noncoding / genetics*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology*
  • Wound Healing / genetics

Substances

  • Biomarkers, Tumor
  • HULC long non-coding RNA, human
  • RNA, Long Noncoding