It is commonly accepted that cellular protein levels are primarily determined by mRNA levels. However, discordance between protein and mRNA expression has been implicated in many pathologic conditions including oncogenesis. The mechanisms involved in this discordance are complicated and far from understood. In this study, it was observed that the expression levels of poly(C) binding protein 2 (PCBP2) mRNA and protein were diametric in breast normal and cancer cell lines, paraffin-embedded and fresh tissue specimens, consistent with data from The Cancer Genome Atlas and the Clinical Proteomic Tumor Analysis Consortium. Moreover, PCBP2 protein expression was significantly associated with disease progression and poor outcome in patients with breast cancer. Depletion of PCBP2 protein inhibited cell proliferation, colony formation, migration, invasion, and in vivo tumor growth and metastasis. Forced expression of PCBP2 exhibited the opposite effect. Mechanistically, it was demonstrated that PCBP2 3′ untranslated region (3′UTR) was subject to alternative splicing and polyadenylation (APA) in breast cancer tissues and cell lines. Non-full-length 3′UTR PCBP2 transcripts yielded more protein than the full-length 3′UTR transcripts and enhanced the oncogenic and metastatic capacities of human breast cancer cells. Furthermore, UFD1 and NT5E were identified as genes downstream of PCBP2. PCBP2 promoted oncogenicity of breast cancer cells via upregulation of the expression of UFD1 and NT5E by direct binding to their 3′UTR-B portions. Implications: Findings demonstrate that APA of PCBP2 3′UTR contributes to its increased expression with subsequent promotion of breast cancer progression by regulating UFD1 and NT5E. Visual Overview: http://mcr.aacrjournals.org/content/molcanres/19/1/86/F1.large.jpg. Visual Overview

中文翻译：

---

PCBP2转录后修饰通过上调UFD1和NT5E诱导乳腺癌进展

人们普遍认为，细胞蛋白质水平主要由 mRNA 水平决定。然而，蛋白质和 mRNA 表达之间的不一致与许多病理状况有关，包括肿瘤发生。这种不一致所涉及的机制很复杂，而且远未得到理解。在这项研究中，观察到 poly(C) 结合蛋白 2 (PCBP2) mRNA 和蛋白质的表达水平在乳腺正常细胞系和癌细胞系、石蜡包埋和新鲜组织标本中是完全不同的，这与癌症基因组的数据一致Atlas 和临床蛋白质组学肿瘤分析联盟。此外，PCBP2 蛋白表达与乳腺癌患者的疾病进展和不良预后显着相关。PCBP2 蛋白的消耗抑制了细胞增殖、集落形成、迁移、侵袭、和体内肿瘤生长和转移。PCBP2的强制表达表现出相反的效果。从机制上讲，已证明 PCBP2 3' 非翻译区 (3'UTR) 在乳腺癌组织和细胞系中发生选择性剪接和多聚腺苷酸化 (APA)。非全长 3'UTR PCBP2 转录物比全长 3'UTR 转录物产生更多的蛋白质，并增强了人类乳腺癌细胞的致癌和转移能力。此外，UFD1 和 NT5E 被确定为 PCBP2 下游的基因。PCBP2 通过直接结合 UFD1 和 NT5E 的 3'UTR-B 部分来上调它们的表达，从而促进了乳腺癌细胞的致癌性。含义：研究结果表明，PCBP2 3'UTR 的 APA 通过调节 UFD1 和 NT5E 促进其表达增加，随后促进乳腺癌进展。视觉概述：http://mcr.aacrjournals.org/content/molcanres/19/1/86/F1.large.jpg。视觉概览