Although earlier studies showed the role of SUB1 in cancer, its mechanistic insight in oncogenesis is not fully understood. The present study shows an increased expression of SUB1 in prostate cancer. Moreover, it is involved in tumorigenesis through the activation of PLK1, BUB1B and C-MYC, and repression of CDKN1B during cancer progression. These proteins are involved in several cellular processes including cell proliferation, cell cycle and tumorigenesis.41, 42, 61, 62 The oncoprotein PLK1 is known to have a role in critical cell cycle events and acts in concert with cyclin-dependent kinase 1-cyclin B1 and Aurora kinases.63 Moreover, in cancer these kinases are often dysregulated, promoting uncontrolled cell proliferation and aberrant cell division.63, 64 The PLK family members have been associated with poor prognosis, which lead to enhanced interest as promising targets for anticancer drug development.65 In our study, we demonstrated that SUB1 positively regulated PLK1 expression at the transcriptional level. Furthermore, we investigated the potential role of SUB1-induced PLK1 in prostate cancer invasion by using PLK1-specific siRNA pool or inhibitor volasertib. The PLK1 inhibitor volasertib attenuated stable RWPE-SUB1 cells ability to proliferate as well as to invade through Matrigel in vitro. Moreover, it is currently the most clinically advanced inhibitor.66 Studies in various cancer cell lines (prostate, lung, colon, melanoma, hematopoietic malignancies and urothelial tumors) demonstrated that volasertib inhibits cell division leading to cell death.67, 68, 69, 70 Additionally, we also observed that SUB1 also regulates BUB1B.