Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
Department of Oncology, Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
Int J Mol Sci. 2023 Aug 19;24(16):12961. doi: 10.3390/ijms241612961.
Potential oncogene cleavage and polyadenylation specific factor 4 (CPSF4) has been linked to several cancer types. However, little research has been conducted on its function in prostate cancer (PCa). In benign, incidental, advanced, and castrate resistant PCa (CRPCa) patient samples, protein expression of CPSF4 was examined on tissue microarray (TMAs) of 353 PCa patients using immunohistochemistry. Using the 'The Cancer Genome Atlas' Prostate Adenocarcinoma (TCGA PRAD) database, significant correlations were found between high CPSF4 expression and high-risk genomic abnormalities such as ERG-fusion, ETV1-fusion, and SPOP mutations. Gene Set Enrichment Analysis (GSEA) of CPSF4 revealed evidence for the increase in biological processes such as cellular proliferation and metastasis. We further examined the function of CPSF4 in vitro and confirmed CPSF4 clinical outcomes and its underlying mechanism. Our findings showed a substantial correlation between Gleason groups and CPSF4 protein expression. In vitro, CPSF4 knockdown reduced cell invasion and migration while also causing G1 and G2 arrest in PC3 cell lines. Our findings demonstrate that CPSF4 may be used as a possible biomarker in PCa and support its oncogenic function in cellular proliferation and metastasis.
潜在的癌基因切割和多聚腺苷酸化特异性因子 4（CPSF4）与几种癌症类型有关。然而，关于其在前列腺癌（PCa）中的功能的研究甚少。在良性、偶发、晚期和去势抵抗性前列腺癌（CRPCa）患者的样本中，使用免疫组织化学在 353 名前列腺癌患者的组织微阵列（TMAs）上检查 CPSF4 的蛋白表达。使用“癌症基因组图谱”前列腺腺癌（TCGA PRAD）数据库，发现 CPSF4 高表达与 ERG 融合、ETV1 融合和 SPOP 突变等高危基因组异常之间存在显著相关性。CPSF4 的基因集富集分析（GSEA）显示出细胞增殖和转移等生物学过程增加的证据。我们进一步在体外研究了 CPSF4 的功能，并证实了 CPSF4 的临床结局及其潜在机制。我们的研究结果表明，Gleason 组与 CPSF4 蛋白表达之间存在显著相关性。在体外，CPSF4 敲低减少了 PC3 细胞系的细胞侵袭和迁移，同时导致 G1 和 G2 期阻滞。我们的研究结果表明，CPSF4 可能可用作前列腺癌的一种可能的生物标志物，并支持其在细胞增殖和转移中的致癌功能。
