XTP8 stimulates migration and invasion of gastric carcinoma through interacting with TGIF1

Eur Rev Med Pharmacol Sci. 2020 Mar;24(5):2412-2420. doi: 10.26355/eurrev_202003_20508.

Abstract

Objective: To determine expression characteristics of XTP8 and TGIF1 in gastric carcinoma (GC), and the potential roles of XTP8/TGIF1 axis in influencing the progression of GC.

Materials and methods: The expression levels of XTP8 and TGIF1 in GC tissues and cells were detected. Their functions in prognosis in GC patients were evaluated by the Kaplan-Meier method. The correlation between the XTP8 level and the pathological indexes of the GC patients were analyzed. The changes in the proliferation, migration, and invasion capacities of MKN-45 and SGC-7901 cells affected by XTP8 and TGIF1 were assessed. The interaction between XTP8 and TGIF1 was determined through Dual-Luciferase reporter gene assay and rescue experiments.

Results: XTP8 was upregulated in GC tissues and cells. XTP8 level was positively correlated with lymphatic and distant metastasis, as well as poor prognosis of GC patients. The silence of XTP8 attenuated proliferation, migration, and invasion capacities of MKN-45 and SGC-7901 cells. TGIF1 was the downstream gene binding to XTP8, which was downregulated in GC, and XTP8 negatively regulated the TGIF1 level in GC tissues. Importantly, the knockdown of TGIF1 could abolish the regulatory effect of XTP8 on GC cell behaviors.

Conclusions: XTP8 is upregulated in GC and is closely linked to lymphatic metastasis, distant metastasis, and poor prognosis of GC patients. Besides, it accelerates the malignant progression via negatively regulating TGIF1.

MeSH terms

  • Cell Movement
  • Cells, Cultured
  • Female
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology

Substances

  • DEPDC1B protein, human
  • GTPase-Activating Proteins
  • Homeodomain Proteins
  • Repressor Proteins
  • TGIF1 protein, human