A new candidate oncogenic lncRNA derived from pseudogene WFDC21P promotes tumor progression in gastric cancer

Cell Death Dis. 2021 Oct 2;12(10):903. doi: 10.1038/s41419-021-04200-x.

Abstract

As oncogenes and tumor suppressor genes, long non-coding RNAs (lncRNAs) regulate the biological behavior of gastric cancer (GC) cells such as proliferation, invasion, and metastasis through various signal pathways. At present, although numerous lncRNAs that significantly influence the development and progression of GC have been identified, a considerable number of them have not been found and studied yet. In this study, we identified a new lncRNA derived from pseudogenes WFDC21P, which have not been reported in any previous GC study. LncRNA WFDC21P was significantly upregulated in GC cells and tissues, and clinically associated with the pathological stages of advanced GC. WFDC21P promoted proliferation and metastasis of GC cells both in vitro and in vivo. LncRNA WFDC21P was directly bound to GTPase Ran and it promoted the activity of the Akt/GSK3β/β-catenin pathway. Forkhead Box P3 (FOXP3), as a transcription factor of WFDC21P, was directly bound to the promoter region and it positively regulated the transcription of WFDC21P. This finding may provide a novel biomarker and therapeutic target for GC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression*
  • Female
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Oncogenes*
  • Protein Binding
  • Pseudogenes*
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology*
  • Subcellular Fractions / metabolism
  • Up-Regulation / genetics
  • ran GTP-Binding Protein / metabolism

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • RNA, Long Noncoding
  • RNA, Messenger
  • ran GTP-Binding Protein