ELK4-mediated lncRNA SNHG22 promotes gastric cancer progression through interacting with EZH2 and regulating miR-200c-3p/Notch1 axis

Cell Death Dis. 2021 Oct 18;12(11):957. doi: 10.1038/s41419-021-04228-z.

Abstract

Long non-coding RNAs (lncRNAs) play important regulatory roles in the initiation and progression of various cancers. However, the biological roles and the potential mechanisms of lncRNAs in gastric cancers remain unclear. Here, we report that the expression of lncRNA SNHG22 (small nucleolar RNA host gene 22) was significantly increased in GC (Gastric Cancer) tissues and cells, which confers poor prognosis of patients. Knockdown of SNHG22 inhibited the proliferation and invasion ability of GC cells. Moreover, we identified that the transcriptional factor, ELK4 (ETS transcription factor ELK4), could promote SNHG22 expression in GC cells. In addition, using RNA pull-down followed MS assay, we found that SNHG22 directly bound to EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) to suppress the expression of tumor suppressor genes. At the same time, SNHG22 sponged miR-200c-3p to increase Notch1 (notch receptor 1) expression. Taken together, our findings demonstrated the role of SNHG22 on promoting proliferation and invasion of GC cells. And we revealed a new regulatory mechanism of SNHG22 in GC cells. SNHG22 is a promising lncRNA biomarker for diagnosis and prognosis and a potential target for GC treatment.

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease Progression*
  • Enhancer of Zeste Homolog 2 Protein / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Genes, Tumor Suppressor
  • Histones / metabolism
  • Humans
  • Lysine / metabolism
  • Methylation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Receptor, Notch1 / metabolism*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology*
  • Up-Regulation / genetics
  • ets-Domain Protein Elk-4 / metabolism*

Substances

  • ELK4 protein, human
  • Histones
  • MIRN200 microRNA, human
  • MicroRNAs
  • NOTCH1 protein, human
  • RNA, Long Noncoding
  • Receptor, Notch1
  • ets-Domain Protein Elk-4
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Lysine