A novel circular RNA, circFAT1(e2), inhibits gastric cancer progression by targeting miR-548g in the cytoplasm and interacting with YBX1 in the nucleus

Cancer Lett. 2019 Feb 1:442:222-232. doi: 10.1016/j.canlet.2018.10.040. Epub 2018 Nov 9.

Abstract

In the present study, two circular RNA (circRNA) expression profiles in paired gastric cancer (GC) tissues from the GEO database were examined. We identified a novel circRNA, has_circ_0001461, which we termed circFAT1(e2). We verified that circFAT1(e2) was significantly downregulated in GC tissues and cell lines and was correlated with overall survival of GC patients. Fluorescence in situ hybridization (FISH) analysis showed that circFAT1(e2) was distributed in the cytoplasm of GC cells, as well as in the nucleus. Functional assays indicated that overexpression of circFAT1(e2) inhibited GC cell proliferation, migration and invasion. Then, we investigated whether circFAT1(e2) acts as a sponge of microRNA-549g(miR-548g) and regulates the expression of tumor suppressor RUNX1 in GC cells. Moreover, we found that nucleus-located circFAT1(e2) could directly interact with Y-box binding protein-1 (YBX1) and inhibit its function. In conclusion, circFAT1(e2) may play a role as a tumor suppressor in GC cells by regulating the miR-548g/RUNX1 axis in the cytoplasm and targeting YBX1 in the nucleus.

Keywords: Gastric cancer; RUNX1; Y-box binding protein-1 (YBX1); circFAT1(e2); miR-548g.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • Core Binding Factor Alpha 2 Subunit / genetics
  • Core Binding Factor Alpha 2 Subunit / metabolism
  • Cytoplasm / genetics
  • Cytoplasm / metabolism
  • Databases, Genetic
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • RNA / genetics
  • RNA / metabolism*
  • RNA, Circular
  • Signal Transduction
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Tumor Burden
  • Y-Box-Binding Protein 1 / genetics
  • Y-Box-Binding Protein 1 / metabolism*

Substances

  • Core Binding Factor Alpha 2 Subunit
  • MIRN548 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RUNX1 protein, human
  • Y-Box-Binding Protein 1
  • YBX1 protein, human
  • RNA