Abstract
BACKGROUND: Esophageal cancer is one of the most common cancers across the globe; the 5-year survival of esophageal cancer patients is still low. MicroRNA (miRNA) dysregulation has been implicated in cancer development, and the miRNAs play a pivotal role in esophageal cancer pathogenesis. It is urgently needed to find out how miRNA dysregulation was involved in esophageal cancer (EC) development. METHODS: Through experiments in vivo and in vitro, we explored potential signaling pathways, miR-493/Wnt5A/c-JUN loop, in EC. Their mechanistic roles in EC cell proliferation, migration, and invasion were investigated through multiple validation steps in EC9706 and TE13 cell lines and EC specimens. RESULTS: Overexpression of miR-493 attenuates esophageal cancer cell proliferation, migration, and invasion in vivo and in vitro. Moreover, miR-493 downregulation is an unfavorable factor in EC and negatively correlated with Wnt5A. The existence of miR-493 is also an important attribute of metabolism. Based on mechanism analyses, we show that miR-493 inhibits the activity of c-JUN and p-PI3K/p-AKT with enhanced p21 and directly regulates Wnt5A expression and function, whereas c-JUN binds the promoter region of miR-493 and suppressed the expression of miR-493, forming a negative feedback loop. CONCLUSIONS: The miR-493/Wnt5A/c-JUN loop is a molecular feedback loop that refers to the development of esophageal cancer cells and a potential target for the treatment of esophageal cancer.