TRIM28 suppresses cancer stem-like characteristics in gastric cancer cells through Wnt/β-catenin signaling pathways.

Abstract

The influences of TRIM28 on the gastric tumorigenesis together with potential molecular mechanisms remain to be studied. We aimed at exploring the important effects of TRIM28 on gastric cancer (GC) and uncovering underling molecular mechanisms. Through immunohistochemistry analysis of 20 pairs of GC and the peritumoral tissues, the expression level of TRIM28 was determined. A variety of assays were applied to explore the important roles of TRIM28 in GC. Western blotting and qRT-PCR analyses were used to analyze the association between TRIM28 and the Wnt/β-catenin signaling pathway. TRIM28 was highly expressed in GC tissues than peritumoral tissues. And high expression level of TRIM28 in GC was associated with good prognostic effects. In vitro functional assays suggested TRIM28 knockdown enhanced the proliferation and clone formation of GC cell. Moreover, TRIM28 knockdown enhanced the expression level of stemness markers, strengthened sphere-forming and drug-resistance properties of GC cells, suggesting important effect on GC cell stemness. Besides, our analysis showed that the Wnt/β-catenin signaling was involved in the effect of TRIM28 on GC cell stemness property, and blocking Wnt/β-catenin signaling pathway obviously rescued the promotion influence of TRIM28 knockdown. Overall, TRIM28 has an important influence on regulating the stem-like property of GC cell via Wnt/β-catenin signaling, suggesting TRIM28 a promising drug target and a potential predictor of prognosis.