Loss-of-function and overexpression studies of MTA1 reinforced its regulatory role in miR-22 expression. MiR-22 directly targets the 3′-untranslated region of E-cadherin, and ectopic overexpression of miR-22 diminishes E-cadherin expression. Overexpression of miR-22 in prostate cancer cells promoted cell invasiveness and migration. Meta-analysis of patient tumor samples indicated a positive correlation between MTA1 and miR-22, supporting their inhibitory effect on E-cadherin expression.
These findings implicate the MTA1/Epi-miR-22/E-cadherin axis as a new epigenetic signaling pathway that promotes tumor invasion in prostate cancer.