LncRNA FEZF1-AS1 Modulates Cancer Stem Cell Properties of Human Gastric Cancer Through miR-363-3p/HMGA2

Abstract

Gastric cancer (GC) is a leading cause of cancer-related death with poor prognosis. Growing evidence has shown that long noncoding ribonucleic acid (lncRNA) FEZ family zinc finger 1 antisense RNA 1(FEZF1-AS1), an “oncogene,” regulates tumor progression and supports cancer stem cell. However, the tumorigenic mechanism of FEZF1-AS1 on gastric cancer stem cell (GCSC) is yet to be investigated. Here, we discovered that FEZF1-AS1 was upregulated in GC tissues and cell lines. Knockdown of FEZF1-AS1 inhibited sphere formation and decreased expression of stem factors and markers. Moreover, FEZF1-AS1 silence also suppressed cell proliferation, viability, invasion, and migration of GCSCs. MiR-363-3p is used as a target of FEZF1-AS1, because its expression was suppressed by FEZF1-AS1 in GCSCs. FEZF1-AS1 could sponge miR-363-3p and increased the expression of high-mobility group AT-hook 2 (HMGA2). The expression of FEZF1-AS1 and miR-363-3p, as well as that of miR-363-3p and HMGA2, was negatively correlated in GC tissues. Finally, FEZF1-AS1 contributed to promotion of GCSCs progression partially through inhibition of miR-363-3p. Subcutaneous xenotransplanted tumor model revealed that silence of FEZF1-AS1 suppressed in vivo tumorigenic ability of GSCS via downregulation of HMGA2. In general, our findings clarified the critical regulatory role of FEZF1-AS1/miR-363-3p/HMGA2 axis in GCSC progression, providing a potential therapeutic target for GC.