Arantes Dos Santos Gabriel, Viana Nayara Izabel, Pimenta Ruan, Reis Sabrina T, Ramos Moreira Leite Katia, Srougi Miguel
Urology Department, Laboratory of Medical Investigation (LIM55), Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil; D'Or Institute for Research and Education (IDOR), Sao Paulo, SP, Brazil.
Urology Department, Laboratory of Medical Investigation (LIM55), Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
Med Hypotheses. 2021 May;150:110566. doi: 10.1016/j.mehy.2021.110566. Epub 2021 Mar 23.
Currently, the biggest challenge for prostate cancer (PCa) is to understand the mechanism by which the disease acquires the castration-resistant phenotype and progresses to a fatal disease. PCa has a high genetic heterogeneity, and cannot be separated into well-defined molecular subtypes. Despite this, there is consensus about the role of the androgen receptor (AR) in all stages of the disease, including the transition to the castration-resistant phenotype. Since AR is a transcription factor, we investigated the possibility of PCa presenting a pattern of global gene expression during disease progression. By analyzing the TCGA and CCLE datasets, we were able to find a pattern of waves of genes being expressed during each stage of disease progression. This phenomenon suggests the existence of a mechanism that globally regulates gene expression, being AR, telomeres, and zinc finger proteins (ZNF), three important players. The AR modulates the telomere biology, and its transcription is regulated by ZNF. Recently, a study suggested that the telomere length might influence the expression of ZNF. Thus, we hypothesized that changes in the triad AR, telomeres, and ZNF control gene expression during the progression of PCa.
目前，前列腺癌（PCa）面临的最大挑战是弄清楚该疾病获得去势抵抗性表型并发展为致命疾病的机制。PCa具有高度的基因异质性，无法被明确划分为分子亚型。尽管如此，对于雄激素受体（AR）在该疾病各个阶段的作用，包括向去势抵抗性表型的转变，人们已达成共识。由于AR是一种转录因子，我们研究了PCa在疾病进展过程中呈现全局基因表达模式的可能性。通过分析TCGA和CCLE数据集，我们发现在疾病进展的每个阶段都存在基因表达波动的模式。这一现象表明存在一种全局调控基因表达的机制，其中AR、端粒和锌指蛋白（ZNF）是三个重要参与者。AR调节端粒生物学，其转录受ZNF调控。最近，一项研究表明端粒长度可能影响ZNF的表达。因此，我们推测在PCa进展过程中，AR、端粒和ZNF三者之间的变化控制着基因表达。
