snoRNP RRP9 Promotes Prostate Cancer Cell Proliferation and Migration via SQSTM1.

Abstract

Small nucleolar RNAs (snoRNAs)-60-300 nucleotide non-coding RNAs are associated with adverse clinical outcomes in cancer patients. However, information on the role of snoRNAs and associated small nuclear ribonucleoprotein (snoRNPs) in prostate cancer (PCa) remains scarce. Here, the contribution of the snoRNP U3 snoRNA-interacting protein 2 (RRP9) in PCa pathogenesis is investigated. A combination of three different shRNAs is employed to knockdown RRP9 in the PCa cell lines DU-145 and PC-3. Cell proliferation is evaluated by seeding cells into a 96-well plates and monitoring daily. Cell migration is evaluated by scratch and Transwell assays. FLAG-RRP9 pull-down, MALDI-TOF/TOF, and co-immunoprecipitation assays are conducted to identify RRP9 binding partners in DU-145 cells. In vitro cell proliferation and migration, as well as in vivo tumor growth, are suppressed following RRP9 knockdown. Pull-down and MALDI-TOF/TOF analyses identified five putative RRP9 binding partners, and co-immunoprecipitation validated that RRP9 interacts with the scaffolding hub protein Sequestome-1 (SQSTM1, p62). Interestingly, SQSTM1 overexpression rescued the anti-growth/migration effects of RRP9 knockdown. This study unveiled a novel oncogenic role for the RRP9-SQSTM1 axis in PCa cells. RRP9 is a snoRNP that binds to SQSTM1, thereby promoting PCa cell proliferation and migration. Targeting the RRP9-SQSTM1 axis may be a viable therapeutic strategy for PCa.