Long intergenic non-coding RNA 00152 promotes tumor cell cycle progression by binding to EZH2 and repressing p15 and p21 in gastric cancer

Oncotarget. 2016 Mar 1;7(9):9773-87. doi: 10.18632/oncotarget.6949.

Abstract

Long noncoding RNAs (lncRNAs) play important regulatory roles in several human cancers. Integrated analysis revealed that expression of long intergenic non-coding RNA 152 (LINC00152) was significantly upregulated in gastric cancer (GC). Further analysis in a cohort of 97 GC patients revealed that LINC00152 expression was positively correlated with tumor invasion depth, lymph node metastasis, higher TNM stage, and poor survival. Gene set enrichment analysis revealed that cell proliferation and cell cycle progression were increased in patients with high LINC00152 expression. In both GC cell lines and xenograft systems, LINC00152 overexpression facilitated GC cell proliferation by accelerating the cell cycle, whereas LINC00152 knockdown had the opposite effect. Moreover, by binding to enhancer of zeste homolog 2 (EZH2), LINC00152 promotes GC tumor cell cycle progression by silencing the expression of p15 and p21. These findings suggest that LINC00152 may play contribute to the progression of GC and may be an effective therapeutic target.

Keywords: LINC00152; cell proliferation; gastric cancer; long non-coding RNA; p15/p21.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cyclin-Dependent Kinase Inhibitor p15 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase Inhibitor p15 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Enhancer of Zeste Homolog 2 Protein / metabolism*
  • Female
  • Humans
  • Lymphatic Metastasis / genetics
  • Male
  • Middle Aged
  • Neoplasm Staging
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA-Binding Proteins / metabolism
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology*

Substances

  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p21
  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • long non-coding RNA Linc00152, human
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein