前列腺癌中 miRNA 介导的 PTEN 基因下调机制的系统综述。
A systematic review of mechanisms of PTEN gene down-regulation mediated by miRNA in prostate cancer.
发表日期:2024 Aug 15
作者:
Fernando Bergez-Hernández, Martín Irigoyen-Arredondo, Alejandra Martínez-Camberos
来源:
Epigenetics & Chromatin
摘要:
磷酸酶和张力蛋白同源基因 (PTEN) 在调节多种细胞过程中至关重要,包括生长、分化、增殖和细胞存活,主要通过调节 PI3K/AKT/mTOR 通路。 PTEN 基因表达的改变与表观遗传机制有关,特别是小非编码 RNA(例如 miRNA)的调节。控制 PTEN 的 miRNA 表达水平的改变已被证明会导致其表达不足。这种低表达反过来会影响 PI3K/AKT/mTOR 通路,从而影响增殖和凋亡等关键机制,在前列腺癌 (PCa) 的发生和进展中发挥重要作用。因此,我们的目的是系统地回顾有关 PCa 中 miRNA 介导的 PTEN 调节的现有信息。搜索电子数据库以识别评估通过 PCa miRNA 进行 PTEN 调节的研究,搜索包括单词 microRNA、PTEN 和前列腺肿瘤的组合。使用 SYRCLE 和 CASP 工具的改编版本对纳入的文章进行质量评估。我们纳入了 39 篇文章,测量 PCa 中 miRNA 的相对基因表达及其与 PTEN 调控的关系。据报道,共有 42 个 miRNA 通过 PTEN 失调参与 PCa 的发生和进展(34 个 miRNA 上调,8 个 miRNA 下调)。 16 个 miRNA 被证明是导致癌变的遗传相互作用的主要调节因子,其中 miR-21 是 PCa 中报道最多的与 PTEN 下调相关的 miRNA。我们发现,miR-200b 和 DNMT1 之间的环或 microRNA 直接靶向 PTEN 可以促进 PTEN 的沉默,从而导致 PI3K/AKT/mTOR 的组成型激活以及与中间基因的相互作用支持细胞凋亡抑制、增殖、侵袭和 PCa 转移。根据我们的综述,主要由 miR-21、-20a、-20b、-93、-106a 和 -106b 上调介导的 PTEN 失调在 PCa 发展中具有核心作用,并且可能具有潜在的潜力用于诊断、预后和治疗目标的生物标志物。© 2024 作者。由爱思唯尔有限公司出版
The Phosphatase and Tensin Homolog gene (PTEN) is pivotal in regulating diverse cellular processes, including growth, differentiation, proliferation, and cell survival, mainly by modulating the PI3K/AKT/mTOR pathway. Alterations in the expression of the PTEN gene have been associated with epigenetic mechanisms, particularly the regulation by small non-coding RNAs, such as miRNAs. Modifications in the expression levels of miRNAs that control PTEN have been shown to lead to its underexpression. This underexpression, in turn, impacts the PI3K/AKT/mTOR pathway, thereby influencing crucial mechanisms like proliferation and apoptosis, playing an important role in the initiation and progression of prostate cancer (PCa). Thus, we aimed to systematically reviewed available information concerning the regulation of PTEN mediated by miRNA in PCa.Electronic databases were searched to identify studies assessing PTEN regulation via PCa miRNAs, the search included combination of the words microRNAs, PTEN and prostatic neoplasms. The quality assessment of the articles included was carried out using an adapted version of SYRCLE and CASP tool.We included 39 articles that measured the relative gene expression of miRNAs in PCa and their relationship with PTEN regulation. A total of 42 miRNAs were reported involved in the development and progression of PCa via PTEN dysregulation (34 miRNAs up-regulated and eight miRNAs down-regulated). Sixteen miRNAs were shown as the principal regulators for genetic interactions leading to carcinogenesis, being the miR-21 the most reported in PCa associated with PTEN down-regulation. We showed the silencing of PTEN could be promoted by a loop between miR-200b and DNMT1 or by direct targeting of PTEN by microRNAs, leading to the constitutive activation of PI3K/AKT/mTOR and interactions with intermediary genes support apoptosis inhibition, proliferation, invasion, and metastasis in PCa.According to our review, dysregulation of PTEN mediated mainly by miR-21, -20a, -20b, -93, -106a, and -106b up-regulation has a central role in PCa development and could be potential biomarkers for diagnosis, prognostic, and therapeutic targets.© 2024 The Authors. Published by Elsevier Ltd.