MiR-498 inhibits autophagy and M2-like polarization of tumor-associated macrophages in esophageal cancer via MDM2/ATF3.

Abstract

Structured abstract Aim: To elucidate the effect of miRNA (miR)-498 on autophagy and M2-like macrophage polarization in esophageal cancer. Methods: Autophagy was evaluated in esophageal cancer. Macrophage markers specific for M1- or M2-like phenotype were determined. The binding relationships between miR-498 and MDM2, MDM2and ATF3 were analyzed. Results: miR-498 was downregulated in esophageal cancer and was associated with disease-free and overall patient survival. Enhanced miR-498 reduced LC3I conversion to LC3II and increased p62 accumulation in KYSE-150 cells, and increased macrophage polarization to M2-like phenotype in KYSE-150 and TAM co-culture. miR-498 inhibited MDM2-mediated ATF3 degradation, thus suppressing autophagy and M2-like polarization of macrophages in esophageal cancer. Conclusion: miR-498 may inhibit autophagy and M2-like polarization of macrophages to suppress esophageal cancer via MDM2/ATF3.