In summary, here we show that reduced miR-101 expression results in transcriptional coactivator SUB1 overexpression (Figure 6f). SUB1 triggers increased cell proliferation, invasion, metastasis and modulates expression of several including PLK1, BUB1B, C-MYC and CDKN1B. Finally, SUB1-mediated oncogenic event can be alleviated using PLK1 siRNA or inhibitor. This study shows SUB1 overexpression in aggressive prostate cancer and reveals therapeutic options to block SUB1-mediated oncogenesis.