Objective: This study aimed to investigate the regulatory effect of lncRNA fetal-lethal non-coding developmental regulatory RNA (FENDRR) on gastric cancer (GC) progression.
Methods: The expression levels of FENDRR in GC tissues and paracancerous tissues, as well as in gastric normal epithelial cell line and GC cell lines were detected. The Ad-FENDRR or si-FENDRR was transfected into AGS and SGC-7901 cells, and cell proliferation, invasion and apoptosis were determined. Online bioinformatics database predicted and screened miR-421 as a potential target of FENDRR, and SIRT3 was predicted as a target gene of miR-421. The pcDNA-SIRT3 or si-SIRT3 was transfected into AGS cells, and cell proliferation, invasion, apoptosis and Notch-1 protein expression were determined. Ad-FENDRR was transfected into AGS and SGC-7901 cells alone or together with miR-421 mimic to explore the effect of miR-421 on cells. The AGS cells transfected with Ad-FENDRR were injected into the armpits of nude mice to establish subcutaneous xenograft tumor model, and tumor growth was observed.
Results: FENDRR expression was downregulated in GC tissues and cell lines. Overexpression of FENDRR or SIRT3 inhibited tumor proliferation and invasion, and promoted apoptosis. The overexpression of Notch-1 reversed the inhibitory effect of SIRT3 on AGS cell. MiR-421 mimic reversed the inhibitory effect of FENDRR on the growth of AGS and SGC-7901 cells. Nude mice injected with FENDRR overexpressing AGS cells had smaller tumor volume and weight and weaker tumor cell proliferation ability.
Conclusion: FENDRR inhibits Notch-1 pathway to inhibit GC cell proliferation and invasion by upregulating SIRT3 expression via targeting miR-421.
Keywords: gastric cancer, lncRNA FENDRR, miR-421, SIRT3, Notch-1 pathway