Park Chan Mi, Lee Jae Eun, Kim Jung Hwa
Department of Biological Sciences, Inha University, Incheon 22212, South Korea.
Genet Mol Biol. 2020 May 8;43(2):e20190328. doi: 10.1590/1678-4685-GMB-2019-0328. eCollection 2020.
BRCA1-associated protein 1 (BAP1) is a deubiquitinating enzyme that has long been considered to be a tumor suppressor in various tumors, including renal cell carcinoma, uveal melanoma, mesothelioma, and cutaneous melanoma. However, the involvement of BAP1 in the progression of prostate cancer has not been studied until recently. Herein, we investigated the tumor promoting function of BAP1 in the context of prostate cancer. Analysis of The Cancer Genome Atlas (TCGA) data set showed that prostate cancer patients express high levels of BAP1 mRNA. High BAP1 expression is inversely correlated with disease-free survival in patients with prostate cancer. Among the prostate cell lines tested, BAP1 expression was high in tumorigenic and metastatic cell lines, but was low in normal prostate cell line. Knockdown of BAP1 in PC3 or DU145 cells induced mesenchymal-to-epithelial transition (MET). Further, BAP1-knockdown resulted in decreased migration and invasion of PC3 and DU145 cells. Conversely, overexpression of BAP1 in RWPE1, a normal prostate cell line, induced the migratory and invasive properties. Collectively, our findings identified that BAP1 has a tumor promoting function in prostate cancer cells, and suggest that BAP1 can serve as a potential therapeutic target for prostate cancer.
乳腺癌1号相关蛋白1(BAP1)是一种去泛素化酶,长期以来一直被认为是包括肾细胞癌、葡萄膜黑色素瘤、间皮瘤和皮肤黑色素瘤在内的多种肿瘤中的肿瘤抑制因子。然而,直到最近BAP1在前列腺癌进展中的作用才得到研究。在此,我们在前列腺癌背景下研究了BAP1的促肿瘤功能。对癌症基因组图谱(TCGA)数据集的分析表明,前列腺癌患者表达高水平的BAP1 mRNA。BAP1高表达与前列腺癌患者的无病生存率呈负相关。在所测试的前列腺细胞系中,BAP1在致瘤性和转移性细胞系中表达较高,但在正常前列腺细胞系中表达较低。在PC3或DU145细胞中敲低BAP1可诱导间充质向上皮转化(MET)。此外,敲低BAP1导致PC3和DU145细胞的迁移和侵袭能力下降。相反,在正常前列腺细胞系RWPE1中过表达BAP1可诱导其迁移和侵袭特性。总的来说,我们的研究结果表明BAP1在前列腺癌细胞中具有促肿瘤功能,并提示BAP1可作为前列腺癌的潜在治疗靶点。