Fig. 7: Proposed model for VMP1 medicated the new feedback regulation mechanism of miR-21 via PTEN/AKT/TFEB pathway in colorectal cancer.

When TFEB was activated and transported into the nuclear in cells, VMP1 transcript was upregulated and VMP1-miR-21 transcript was down-regulated, Meanwhile, pri-miR-21 transcript was also reduced due to the binding of transcription factors to pri-miR-21 promoter were blocked by TFEB-induced high transcriptional activation of VMP1, such as STAT3 (dashed lines). When VMP1 transcription was inhibited by TFEB phosphorylation, both VMP1-miR-21 and pri-miR-21 transcripts were increased. Subsequently, the high expression of miR-21 increased phosphorylation of AKT by inhibiting PTEN, and then phosphorylated AKT promoted phosphorylation of TFEB and repressed its nuclear translocation, leading to VMP1 transcription was further inhibited and miR-21 transcription was further increased (solid lines).