Shahrouzi Parastoo, Astobiza Ianire, Cortazar Ana R, Torrano Verónica, Macchia Alice, Flores Juana M, Niespolo Chiara, Mendizabal Isabel, Caloto Ruben, Ercilla Amaia, Camacho Laura, Arreal Leire, Bizkarguenaga Maider, Martinez-Chantar Maria L, Bustelo Xose R, Berra Edurne, Kiss-Toth Endre, Velasco Guillermo, Zabala-Letona Amaia, Carracedo Arkaitz
Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160 Derio, Spain.
CIBERONC (Centro de Investigación Biomédica en Red de Cáncer), 28029 Madrid, Spain.
Cancers (Basel). 2020 Sep 11;12(9):2593. doi: 10.3390/cancers12092593.
Prostate cancer is the most frequent malignancy in European men and the second worldwide. One of the major oncogenic events in this disease includes amplification of the transcription factor cMYC. Amplification of this oncogene in chromosome 8q24 occurs concomitantly with the copy number increase in a subset of neighboring genes and regulatory elements, but their contribution to disease pathogenesis is poorly understood. Here we show that is among the most robustly upregulated coding genes within the 8q24 amplicon in prostate cancer. Moreover, we demonstrate that amplification and overexpression are frequent in this tumor type. Importantly, we find that, parallel to its amplification, transcription is controlled by cMYC. Mouse modeling and functional analysis revealed that aberrant TRIB1 expression is causal to prostate cancer pathogenesis. In sum, we provide unprecedented evidence for the regulation and function of TRIB1 in prostate cancer.
前列腺癌是欧洲男性中最常见的恶性肿瘤，在全球范围内位列第二。该疾病的主要致癌事件之一包括转录因子cMYC的扩增。8号染色体q24区域中该致癌基因的扩增与一部分相邻基因和调控元件的拷贝数增加同时发生，但其对疾病发病机制的作用仍知之甚少。在此，我们表明[基因名称]是前列腺癌8q24扩增子中上调最为显著的编码基因之一。此外，我们证明该基因的扩增和过表达在这种肿瘤类型中很常见。重要的是，我们发现，与其扩增并行，[基因名称]的转录受cMYC控制。小鼠建模和功能分析表明，TRIB1的异常表达是前列腺癌发病机制的原因。总之，我们为TRIB1在前列腺癌中的调控和功能提供了前所未有的证据。 （注：原文中部分基因名称未给出具体内容，用[基因名称]代替）
