累积证据表明RNA调控在癌症中的重要性。这包括剪接、翻译和非编码RNA的调控等事件，这些功能由RNA结合蛋白(RBPs)调控。为了找出哪些RBPs可能与前列腺癌相关，我们对临床前列腺癌中的RBP表达进行了系统筛查。我们调查了四个全蛋白组学数据集，包括原发性肿瘤样本、去势抵抗性和转移性前列腺癌。我们发现，尽管大部分RBPs在前列腺癌的发展和进展过程中表达但没有显著改变，但其中几种RBP的表达在晚期疾病中增加。有趣的是，大部分差异表达的RBPs在疾病进展过程中并不是差异性转录后磷酸化的目标。发生表达变化的RBPs在多聚(A)-RNA结合、核质转运和细胞应激反应等方面具有功能，这表明它们可能在留葛胺抵抗的形成中起作用。途径分析表明，增加的核糖体生产和RBPs与染色质相关的功能也与留葛胺抵抗和转移性前列腺癌有关。我们选择了一组差异表达的RBPs并研究了它们在培养的前列腺癌细胞中的作用。通过siRNA筛选，我们发现其中几种在前列腺癌细胞的存活（DDX6、EIF4A3、PABPN1）、生长（如EIF5A、HNRNPH2、LRRC47和NVL）和迁移（如NOL3和SLTM）中发挥作用。我们的分析进一步表明，在前列腺癌的转移过程中，RRP9这种对核糖体形成至关重要的U3小核糖体蛋白在蛋白水平上发生了改变。在这项研究中，我们确定了前列腺癌发展和演变过程中RBP谱的显著分子变化。我们的研究进一步显示了几种具有重要功能的RBPs，值得进一步研究它们在前列腺癌中的功能和可能的靶向性。© 2023 The Authors. Cancer Reports published by Wiley Periodicals LLC.

Accumulating evidence indicates importance of RNA regulation in cancer. This includes events such as splicing, translation, and regulation of noncoding RNAs, functions which are governed by RNA binding proteins (RBPs).To find which RBPs could be relevant for prostate cancer, we performed systematic screening of RBP expression in clinical prostate cancer.We interrogated four proteome-wide proteomics datasets including tumor samples of primary, castration resistant, and metastatic prostate cancer. We found that, while the majority of RBPs are expressed but not significantly altered during prostate cancer development and progression, expression of several RBPs increases in advanced disease. Interestingly, most of the differentially expressed RBPs are not targets of differential posttranscriptional phosphorylation during disease progression. The RBPs undergoing expression changes have functions in, especially, poly(A)-RNA binding, nucleocytoplasmic transport, and cellular stress responses, suggesting that these may play a role in formation of castration resistance. Pathway analyzes indicate that increased ribosome production and chromatin-related functions of RBPs are also linked to castration resistant and metastatic prostate cancers. We selected a group of differentially expressed RBPs and studied their role in cultured prostate cancer cells. With siRNA screens, several of these were indicated in survival (DDX6, EIF4A3, PABPN1), growth (e.g., EIF5A, HNRNPH2, LRRC47, and NVL), and migration (e.g., NOL3 and SLTM) of prostate cancer cells. Our analyzes further show that RRP9, a U3 small nucleolar protein essential for ribosome formation, undergoes changes at protein level during metastasis in prostate cancer.In this work, we recognized significant molecular alterations in RBP profiles during development and evolution of prostate cancer. Our study further indicates several functionally significant RBPs warranting further investigation for their functions and possible targetability in prostate cancer.© 2023 The Authors. Cancer Reports published by Wiley Periodicals LLC.