FOXC2-AS1 stabilizes FOXC2 mRNA via association with NSUN2 in gastric cancer cells

Hum Cell. 2021 Nov;34(6):1755-1764. doi: 10.1007/s13577-021-00583-3. Epub 2021 Jul 29.

Abstract

Long noncoding RNA (lncRNA) FOXC2-AS1 has been reported to act as an oncogene in multiple human cancers. However, the clinical significance, functional role and underlying mechanism of FOXC2-AS1 in gastric cancer (GC) remains largely unknown. Here, we found that FOXC2-AS1 expression was significantly elevated in GC tissues and cells, and overexpression of FOXC2-AS1 indicated advanced TNM stage and shorter overall survival in GC patients. Functionally, knockdown of FOXC2-AS1 attenuated the proliferation, migration and invasion of GC cells, whereas overexpression of FOXC2-AS1 showed the opposite effects. Further investigation revealed that FOXC2-AS1 interacted with FOXC2 mRNA and repressed its degradation. FOXC2-AS1 recruited RNA methyltransferase NSUN2 to FOXC2 mRNA, increasing its m5C level and association with YBX1. Taken together, our findings suggested that FOXC2-AS1 acted as an oncogenic lncRNA by stabilizing FOXC2 mRNA in an m5C-dependent manner, which may provide a novel therapeutic target for GC.

Keywords: NSUN2; RNA stability; YBX1; m5C modification.

MeSH terms

  • Cell Line
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Forkhead Transcription Factors* / metabolism
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Methyltransferases / metabolism*
  • Molecular Targeted Therapy
  • Neoplasm Invasiveness / genetics
  • Neoplasm Staging
  • Oncogenes*
  • RNA, Long Noncoding*
  • RNA, Messenger* / metabolism
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology*
  • Stomach Neoplasms / therapy
  • Survival Rate

Substances

  • Forkhead Transcription Factors
  • RNA, Long Noncoding
  • RNA, Messenger
  • mesenchyme fork head 1 protein
  • Methyltransferases
  • NSUN2 protein, human