Downregulation of contributes to prostate cancer cell invasion and TGFβ1-induced EMT.

Epithelial-to-mesenchymal transition (EMT) activation is important in cancer progression and metastasis. Evidence indicates that is a representative Pol III gene that processes microRNA products via Dicer and further downregulates its target gene transforming growth factor- β1 (TGF-β1), which is the most prominent inducer of EMT in prostate cancer (PC). Consistent with the previous literature, we found that downregulation was strongly associated with metastatic behavior and showed worse outcomes in PC patients. However, little is known about the association between and the EMT signaling pathway. We developed a PC cell model with stable overexpression of and found that changed cellular morphology and drove MET. The underlying mechanism may be related to its promotion of SNAIL protein degradation via ubiquitination, but not to its neighboring genes, TGFβ-induced protein () and , which are Pol II-transcribed. TGF-β1 also override nc886 promotion of MET via transient suppression the transcription of , promotion of or increase in SMAD5 phosphorylation. Both inhibition and activation occur regardless of their methylation status. The literature suggests that MYC inhibition by TGF-β1 is attributed to downregulation. We incidentally identified MYC-associated zinc finger protein (MAZ) as a suppressive transcription factor of TGFBI, which is controlled by TGF-β1. We elucidate a new mechanism of TGF-β1 differential control of Pol II and the transcription of its neighboring Pol III gene and identify a new EMT unit consisting of and its neighboring genes.