NTF4 stimulates the progression of gastric cancer via regulating FOXL1

To elucidate the diagnostic and prognostic potentials of NTF4 in gastric cancer (GC), as well as its regulatory effects on biological functions of GC cells.

Fifty-two GC patients treated by surgical resection were retrospectively analyzed and their cancer and adjacent tissues were collected. NTF4 levels in GC tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between NTF4 and clinical features of GC was analyzed. After knockdown of NTF4, the proliferative and migratory abilities of MKN45 and BGC-823 cells, and growth rate of GC in nude mice were examined. In addition, the target gene of NTF4, FOXL1 was confirmed by dual-luciferase reporter assay, and co-regulation on GC process was determined by rescue experiments.

NTF4 was upregulated in GC tissues than in normal ones. High level of NTF4 predicted malignant progression, poor overall survival and progression-free survival in GC patients. Knockdown of NTF4 attenuated the in vitro proliferative and migratory abilities of GC cells, as well as in vivo tumorigenicity of GC in nude mice. FOXL1 was the target gene of NTF4, which was lowly expressed in GC. Knockdown of FOXL1 was able to reverse the influence of silenced NTF4 on the biological functions of GC cells.

NTF4 is an effectively diagnostic biomarker for early-stage GC, and it stimulates the proliferative and migratory potentials in GC by negatively regulating FOXL1.