■磷酸酶和Tensin同源基因(PTEN)在调节多种细胞过程中至关重要,包括增长,分化,扩散,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。特别是小的非编码RNA的调控,如miRNA。已显示控制PTEN的miRNA表达水平的修饰导致其表达不足。这种减压,反过来,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)的发生和发展中起着重要作用。因此,我们旨在系统回顾有关miRNA在PCa中介导的PTEN调控的现有信息。
■搜索电子数据库以确定通过PCamiRNA评估PTEN调节的研究,搜索包括microRNA的组合,PTEN和前列腺肿瘤。所包括的文章的质量评估是使用SYRCLE和CASP工具的改编版本进行的。
■我们包括39篇文章,这些文章测量了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种miRNA通过PTEN失调参与PCa的发展和进展(34种miRNA上调,8种miRNA下调)。16个miRNAs被证明是导致癌症发生的遗传相互作用的主要调节因子。作为与PTEN下调相关的PCa中报道最多的miR-21。我们显示PTEN的沉默可以通过miR-200b和DNMT1之间的环或通过microRNA直接靶向PTEN来促进,导致PI3K/AKT/mTOR的组成型激活和与中间基因的相互作用支持凋亡抑制,扩散,入侵,和PCa的转移。
■根据我们的评论,PTEN的失调主要由miR-21、-20a、-20b,-93,-106a,和-106b上调在PCa的发展中起着核心作用,可能是诊断的潜在生物标志物,预后,和治疗目标。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.