Long non-coding RNA IRAIN suppresses apoptosis and promotes proliferation by binding to LSD1 and EZH2 in pancreatic cancer

Tumour Biol. 2016 Nov;37(11):14929-14937. doi: 10.1007/s13277-016-5380-8. Epub 2016 Sep 19.

Abstract

Long non-coding RNA (lncRNA) modulates gene expression, while lncRNA dysregulation is associated with human cancer. Furthermore, while recent studies have shown that lncRNA IRAIN plays an important role in other malignancies, the role of IRAIN in pancreatic cancer (PC) progression remains unclear. In this study, we found that upregulation of lncRNA IRAIN was significantly correlated with tumor size, TNM stage, and lymph node metastasis in a cohort of 37 PC patients. In vitro experiments showed that knockdown of IRAIN by small interfering RNA (siRNA) significantly induced cell apoptosis and inhibited cell proliferation in both BxPC-3 and PANC-1 cells. Further mechanism study showed that, by binding to histone demethylase lysine-specific demethylase 1 (LSD1), an enhancer of zeste homolog 2 (EZH2), IRAIN reduced PC tumor cell apoptosis and induced growth arrest by silencing the expression of Kruppel-like factor 2 (KLF2) and P15. Moreover, IRAIN expression was inversely correlated with that of KLF2 and P15 in PC tissues. To our knowledge, this is the first report elucidating the role and mechanism of IRAIN in PC progression.

Keywords: Apoptosis; EZH2; IRAIN; LSD1; Pancreatic cancer; lncRNA.

MeSH terms

  • Apoptosis / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Cyclin-Dependent Kinase Inhibitor p15 / biosynthesis
  • Cyclin-Dependent Kinase Inhibitor p15 / genetics
  • Enhancer of Zeste Homolog 2 Protein / metabolism*
  • Female
  • Histone Demethylases / metabolism*
  • Humans
  • Kruppel-Like Transcription Factors / biosynthesis
  • Kruppel-Like Transcription Factors / genetics
  • Lymphatic Metastasis / genetics
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • RNA Interference
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Small Interfering / genetics
  • RNA-Binding Proteins / metabolism

Substances

  • CDKN2B protein, human
  • Cyclin-Dependent Kinase Inhibitor p15
  • KLF2 protein, human
  • Kruppel-Like Transcription Factors
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Histone Demethylases
  • KDM1A protein, human
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein