Predictive Oncology Laboratory, Centre de Recherche en Cancérologie de Marseille, Inserm UMR 1068, CNRS UMR 7258, Institut Paoli-Calmettes, Aix-Marseille University, 27 Bd. Leï Roure, F-13009 Marseille, France.
Laboratory of Biochemistry and Molecular Biology, Science University of Tunis, 2092, El Manar, Tunis, Tunisia.
Oncogene. 2022 Jan;41(1):125-137. doi: 10.1038/s41388-021-02039-2. Epub 2021 Oct 28.
Disease progression and therapeutic resistance of prostate cancer (PC) are linked to multiple molecular events that promote survival and plasticity. We previously showed that heat shock protein 27 (HSP27) acted as a driver of castration-resistant phenotype (CRPC) and developed an oligonucleotides antisense (ASO) against HSP27 with evidence of anti-cancer activity in men with CRPC. Here, we show that the tumor suppressor Menin (MEN1) is highly regulated by HSP27. Menin is overexpressed in high-grade PC and CRPC. High MEN1 mRNA expression is associated with decreased biochemical relapse-free and overall survival. Silencing Menin with ASO technology inhibits CRPC cell proliferation, tumor growth, and restores chemotherapeutic sensitivity. ChIP-seq analysis revealed differential DNA binding sites of Menin in various prostatic cells, suggesting a switch from tumor suppressor to oncogenic functions in CRPC. These data support the evaluation of ASO against Menin for CRPC.
前列腺癌（PC）的疾病进展和治疗耐药性与多种促进生存和可塑性的分子事件有关。我们之前的研究表明，热休克蛋白 27（HSP27）是去势抵抗表型（CRPC）的驱动因素，并开发了一种针对 HSP27 的寡核苷酸反义（ASO），在患有 CRPC 的男性中具有抗癌活性。在这里，我们表明肿瘤抑制因子 Menin（MEN1）受 HSP27 高度调控。Menin 在高级 PC 和 CRPC 中过表达。高 MEN1 mRNA 表达与生化无复发生存和总生存时间缩短相关。用 ASO 技术沉默 Menin 可抑制 CRPC 细胞增殖、肿瘤生长，并恢复化疗敏感性。ChIP-seq 分析显示 Menin 在各种前列腺细胞中的差异 DNA 结合位点，表明其在 CRPC 中从肿瘤抑制因子转变为致癌功能。这些数据支持对 CRPC 进行 Menin ASO 的评估。
Zotero 插件
