MiR-22 Suppresses EMT by Mediating Metabolic Reprogramming in Colorectal Cancer through Targeting MYC-Associated Factor X

Abstract

Colorectal cancer (CRC) is one of the most frequent gastrointestinal cancers. MicroRNAs (miRNAs) have been proved to be unusually expressed in CRC progression and thus alter multiple pathological processes in CRC cells. However, the specific roles and mechanisms of miR-22 in CRC have not been clearly reported. MicroRNA-22 (miR-22) and MYC-associated factor X (MAX) expressions were determined by RT-qPCR in CRC tissues and cells. The targeted regulatory effects of miR-22 and MAX were confirmed by luciferase reporter and coimmunoprecipitation assays. Also, gain- and loss-of-function and rescue experiments were used to elucidate the function and mechanism of miR-22 and MAX in CRC cells and the mouse xenograft model. We discovered that miR-22 was hypermethylated and downregulated, while MAX was upregulated in CRC. miR-22 markedly inhibited migration, invasion, glycolysis, and cancer stem cell transcription factors in CRC cells. In addition, it was found that miR-22 can directly target MAX. Additional functional experiments confirmed that MAX overexpression can rescue the effects of miR-22 on the behavior of CRC cells. This study suggested that miR-22, as a cancer suppressor, participates in CRC progression by targeting MAX, which might provide basic information for therapeutic targets for CRC.