Zhang Ming-Peng, Zhang Wei-San, Tan Jin, Zhao Ming-Hui, Lian Lin-Juan, Cai Jie
Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute Tianjin 300052, China.
Am J Transl Res. 2017 Feb 15;9(2):708-714. eCollection 2017.
Poly r(C) binding protein (PCBP) 1 or heterogeneous ribonucleoprotein (hnRNP) E1 is a RNA binding protein that plays a vital role in a wide variety of biological processes. PCBP1 has been shown to function as a tumor suppressor by negatively regulating translation of pro-metastatic proteins in different cancers. Loss of expression or its Akt2-mediated phosphorylation at serine 43 residue has both been indicated to de-repress its regulation of EMT inducer proteins. Our previous work has established that functions as a tumor suppressor in thyroid cancer, where its translation is inhibited by microRNA-490-3p. Here we show that thyroid cancer patients can be divided into 2 cohorts based on miR-490-3p expression and mRNA expression-one cohort with high mRNA expression and basal miR-490-3p expression and a second cohort with low mRNA expression and high miR-490-3p expression. However, PCBP1 protein expression is also downregulated in the cohort with high PCBP1 mRNA expression, with expression levels similar to what is observed in patients with the low PCBP1 mRNA expression. Our analysis shows that mRNA is actively translated in patients with high mRNA expression, but that the protein is post translationally degraded by the proteasome machinery. Our results thus elucidate a novel mechanism responsible for down regulation of PCBP1 expression in thyroid cancer. It will be important in future to identify the mechanism that causes degradation of PCBP1 protein and to identify if similar mechanisms are active in other tumors characterized by low PCBP1 protein expression.
多聚胞嘧啶结合蛋白（PCBP）1或异质核糖核蛋白（hnRNP）E1是一种RNA结合蛋白，在多种生物学过程中发挥着至关重要的作用。PCBP1已被证明在不同癌症中通过负调控促转移蛋白的翻译而发挥肿瘤抑制作用。其表达缺失或丝氨酸43残基处的Akt2介导的磷酸化均已表明会解除其对上皮-间质转化诱导蛋白的调控。我们之前的工作已证实其在甲状腺癌中作为肿瘤抑制因子发挥作用，在甲状腺癌中其翻译受到微小RNA-490-3p的抑制。在这里我们表明，甲状腺癌患者可根据miR-490-3p表达和PCBP1 mRNA表达分为两个队列——一个队列PCBP1 mRNA表达高且基础miR-490-3p表达，另一个队列PCBP1 mRNA表达低且miR-490-3p表达高。然而，在PCBP1 mRNA表达高的队列中，PCBP1蛋白表达也下调，其表达水平与PCBP1 mRNA表达低的患者中观察到的相似。我们的分析表明，在PCBP1 mRNA表达高的患者中，PCBP1 mRNA被积极翻译，但该蛋白在翻译后被蛋白酶体机制降解。因此，我们的结果阐明了甲状腺癌中PCBP1表达下调的一种新机制。未来确定导致PCBP1蛋白降解的机制以及确定类似机制在其他以PCBP1蛋白表达低为特征的肿瘤中是否活跃将很重要。
