LncRNA IGFL2-AS1 functions as a ceRNA in regulating ARPP19 through competitive binding to miR-802 in gastric cancer

Mol Carcinog. 2020 Mar;59(3):311-322. doi: 10.1002/mc.23155. Epub 2020 Jan 13.

Abstract

Gastric cancer (GC) is one of the most common malignancies of the digestive system worldwide. Multiple long noncoding RNAs (lncRNAs) participate in the regulation of GC development and metastasis. In this study, we aimed to elucidate the expression and function of lncRNA IGFL2-AS1 in GC. We found that IGFL2-AS1 was highly expressed in GC tissues and cell lines. Knockdown of IGFL2-AS1 suppressed GC cell proliferation, migration, and invasion in vitro. Furthermore, we identified that IGFL2-AS1 exerted its function as a molecular sponge of miR-802. MiR-802 was demonstrated to be a tumor suppressor, and overexpression of miR-802 suppressed GC cell growth, migration, and invasion. Mechanistically, we revealed that the cAMP-regulated phosphoprotein 19 (ARPP19) was a direct target of miR-802 and could reverse the inhibitory function of miR-802. Moreover, our results confirmed that knockdown of IGFL2-AS1 inhibited GC tumor development in an in vivo GC tumor xenograft model. In summary, our data suggest that the IGFL2-AS1/miR-802/ARPP19 axis plays a critical role in the progression and metastasis of GC. Therapies targeting the IGFL2-AS1/miR-802/ARPP19 axis can potentially improve GC treatment.

Keywords: ARPP19; IGFL2-AS1; gastric cancer; miR-802.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Phosphoproteins / genetics*
  • RNA, Long Noncoding / genetics*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology

Substances

  • MIRN802 microRNA, human
  • MicroRNAs
  • Phosphoproteins
  • RNA, Long Noncoding
  • cyclic AMP-regulated phosphoprotein 19