Overexpression of USP39 predicts poor prognosis and promotes tumorigenesis of prostate cancer via promoting EGFR mRNA maturation and transcription elongation

Abstract

Castration resistance is a serious problem facing clinical treatment of prostate cancer (PCa). The underlying molecular mechanisms of acquired proliferation ability of tumor cells upon androgen deprivation are largely undetermined. In the present study, we identified that ubiquitin specific peptidase 39 (USP39) was significantly upregulated in PCa samples and cell lines. Elevated USP39 expression was positively correlated with Gleason score, predicted a poor outcome, and functioned as an independent risk factor for biochemical recurrence (BCR) especially in patients with a Gleason score ≤7. Our cell-based study showed that the expression level of USP39 was the highest in AR-negative PCa cell lines. Knockdown of USP39 in PCa cells inhibited cancer colony formation and tumor cell growth, and induced G2/M arrest and cell apoptosis. Microarray analysis suggested that knockdown of USP39 caused a reduced expression of EGFR. Silencing of USP39 inhibited the expression of EGFR 3′-end, and presented a remarkable block to the maturation of EGFR mRNA, suggesting that silencing of USP39 decreased the transcriptional elongation and maturation of EGFR mRNA. Oncomine datasets analysis showed that USP39 expression was positively correlated with EGFR level. The above findings suggest that USP39 plays a vital oncogenic role in the tumorigenesis of PCa and may prove to be a potential biomarker for predicting the prognosis of PCa patients.

Downregulation of USP32 inhibits cell proliferation, migration and invasion in human small cell lung cancer

“…. These results were also in agreement with the role of USP39, and also belongs to the USPs family in tumour progression, such as hepatocellular carcinoma and prostate cancer . However, further investigation was still needed to confirm whether this well‐characterized DUB activity of USP32 knockdown altered cell cycle and apoptosis regulatory‐related proteins via direct transcriptional or post‐translational regulation in the cell proliferation machinery of SCLC cells.…”

Ubiquitin‑specific protease 7 promotes osteosarcoma cell metastasis by inducing epithelial‑mesenchymal transition

“…DUBs catalyse the removal of ubiquitin and polyubiquitin chains from the target protein (8). Ubiquitin-specific proteases (USPs) constitute the largest subgroup of DUBs and are involved in the development of many cancers by upregulating various key oncoproteins (9)(10)(11).…”

USP39 promotes colorectal cancer growth and metastasis through the Wnt/β-catenin pathway

“…Similarly, USP39 mutation in breast cancer cells, also implicate it as an oncogenic factor, and its downregulation induced apoptosis of the MCF-7 breast tumor cells (9). A study (10) has further demonstrated that USP39 overexpression enhanced the proliferation of prostate cancer cells, thereby suggesting that USP39 may also play a key role in prostate cancer development. All these studies have emphasized that USP39 may be a potential molecular target of cancer.…”