microRNA-497-mediated Smurf2/YY1/HIF2α axis in tumor growth and metastasis of esophageal squamous cell carcinoma

Aberrant expression of microRNA-497 (miR-497) is associated with tumor progression, but the molecular mechanisms in tumorigenesis remain largely unknown. Here, we report that miR-497 expression is downregulated in esophageal squamous cell carcinoma (ESCC) clinical samples. Consistently, upregulation of miR-497 inhibits ESCC cell malignant properties and tumor growth in vivo. Importantly, we uncovered that miR-497 upregulation suppressed ESCC cell growth and tumor growth by inhibiting Smurf2. Mechanistically, we showed that Smurf2 was a target of miR-497, and mediated YY1 expression to elevate HIF2 alpha expression, thereby enhancing the malignancy of ESCC cells. Together, our study uncovered the role of the miR-497-mediated Smurf2/YY1/HIF2 alpha axis in tumor growth and metastasis, which might provide potential therapeutic targets for human ESCC.