Long non-coding RNA Linc00152 is involved in cell cycle arrest, apoptosis, epithelial to mesenchymal transition, cell migration and invasion in gastric cancer

Cell Cycle. 2015;14(19):3112-23. doi: 10.1080/15384101.2015.1078034. Epub 2015 Aug 3.

Abstract

Gastric cancer remains a serious threat to public health with high incidence and mortality worldwide. Accumulating evidence demonstrates that long non-coding RNAs (lncRNAs) play important roles in regulating gene expression and are involved in various pathological processes, including gastric cancer. To investigate the possible role of dysregulated lncRNAs in gastric cancer development, we performed lncRNA microarray and identified 3141 significantly differentially expressed lncRNAs in gastric cancer tissues. Next, some of deregulated lncRNAs were validated among about 60 paired gastric cancer specimens such as Linc00261, DKFZP434K028, RPL34-AS1, H19, HOTAIR and Linc00152. Our results found that the decline of DKFZP434K028 and RPL34-AS1, and the increased expression of Linc00152 positively correlated with larger tumor size. The high expression levels of HOTAIR were associated with lymphatic metastasis and poor differentiation. Since the biological roles of Linc00152 are largely unknown in gastric cancer pathogenesis, we assessed its functions by silencing its up-regulation in gastric cancer cells. We found that Linc00152 knockdown could inhibit cell proliferation and colony formation, promote cell cycle arrest at G1 phase, trigger late apoptosis, reduce the epithelial to mesenchymal transition (EMT) program, and suppress cell migration and invasion. Taken together, we delineate the gastric cancer lncRNA signature and demonstrate the oncogenic functions of Linc00152. These findings may have implications for developing lncRNA-based biomarkers for diagnosis and therapeutics for gastric cancer.

Keywords: EMT; apoptosis; cell cycle; cell migration and invasion; gastric cancer; lncRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics*
  • Apoptosis / physiology
  • Cell Cycle Checkpoints / genetics*
  • Cell Cycle Checkpoints / physiology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Movement / physiology*
  • Cell Proliferation / genetics*
  • Cell Proliferation / physiology
  • Computational Biology
  • Epithelial-Mesenchymal Transition / genetics*
  • Epithelial-Mesenchymal Transition / physiology
  • Flow Cytometry
  • Humans
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / physiology
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / physiopathology

Substances

  • RNA, Long Noncoding