In this study, we identified a novel feedback loop regulating miR-21 expression, in which miR-21 inhibits the expression of VMP1 through the PTEN/TFEB pathway in CRC cells, which in turn directly negatively regulates miR-21 expression by transcriptional repression, thus forming a feedback loop, miR-21/VMP1. This evidence concerns the gene VMP1 and colorectal carcinoma.