LncRNA DLEU2 is activated by STAT1 and induces gastric cancer development via targeting miR-23b-3p/NOTCH2 axis and Notch signaling pathway

Life Sci. 2021 Jul 15:277:119419. doi: 10.1016/j.lfs.2021.119419. Epub 2021 Mar 27.

Abstract

Introduction: Gastric cancer (GC) has severely affected the health of patients and caused high mortality around the world. Long non-coding RNAs (lncRNAs) have been validated to play significant roles in biological process of multiple cancers.

Methods: Quantitative real-time PCR (RT-qPCR) and western blot analysis were conducted to evaluate the expression levels and protein levels of related genes in GC cells. Functional assays were implemented to explore the effect of deleted in lymphocytic leukemia 2 (DLEU2). The upstream and downstream mechanisms of DLEU2 were verified by mechanism investigations.

Results: The expression of long non-coding RNA (lncRNA) DLEU2 was observably high in GC cells and tissues. DLEU2 silence depressed the capacities of proliferation, migration and invasion but promoted apoptosis in GC cells. Moreover, DLEU2 was activated by signal transducer and activator of transcription 1 (STAT1) and sequestered microRNA-23b-3p (miR-23b-3p) to modulate the expression of notch receptor 2 (NOTCH2), thereby stimulating Notch signaling pathway. More importantly, DLEU2 contributed to GC progression via targeting miR-23b-3p/NOTCH2 axis.

Conclusions: In summary, our research identified the STAT1/DLEU2/miR-23b-3p/NOTCH2/Notch axis in GC development, indicating that DLEU2 might function as a novel biomarker in GC.

Keywords: DLEU2; Gastric cancer; NOTCH2; STAT1; miR-23b-3p.

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics
  • RNA, Long Noncoding / genetics*
  • Receptor, Notch2 / genetics
  • Receptor, Notch2 / metabolism*
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / metabolism*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • DLEU2 lncRNA, human
  • MIRN23b microRNA, human
  • MicroRNAs
  • NOTCH2 protein, human
  • RNA, Long Noncoding
  • Receptor, Notch2
  • STAT1 Transcription Factor
  • STAT1 protein, human