Ursolic acid suppresses gastric cancer by targeting the miR-27a-3p/Wnt/β-catenin signaling axis

Gastric cancer (GC) is a common type of cancer known for its challenges in early detection and unfavorable prognosis. The pathway involving Wnt/β-catenin and the improper regulation of microRNAs (miRNAs), especially miR-27a-3p, are crucial in the advancement of GC. Ursolic acid (UA), which is a naturally occurring anticancer agent, shows promise in the inhibition of GC. Although UA's anticancer effects have been recognized, the underlying molecular mechanisms in GC remain incompletely defined. Our findings indicate that UA strongly restricts the expansion, motility, and invasive behavior of GC cells by dampening activity within the Wnt/β-catenin cascade. Treatment with UA lowered miR-27a-3p expression, and blocking this miRNA further curtailed tumor cell aggressiveness by restoring DKK2, which functions as a suppressor of Wnt-driven signaling. The protein under investigation showed lower expression in advanced tumors. Its expression in these advanced tumors correlated with better pathologic outcomes and survival prognosis. Thus, we can categorize this protein as a novel tumor suppressor in GC. Consistent with these in vitro results, in vivo assays demonstrated that UA effectively curtailed tumor development. Taken together, these findings indicate that UA restricts GC progression via modulation of the miR-27a-3p/DKK2/Wnt/β-catenin axis, providing mechanistic insights for potential therapeutic strategies.