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微小RNA 34-a调节子宫内膜异位症中SIRT-1和Foxo-1的表达。

MiRNA 34-a regulate SIRT-1 and Foxo-1 expression in endometriosis.

作者信息

Rezk Noha A, Lashin Mohamad Bakry, Sabbah Norhan A

机构信息

Medical Biochemistry Department, Faculty of Human Medicine, Zagazig University, Zagazig, Egypt.

Gynecology & Obstetrics Department, Faculty of Human Medicine, Zagazig University, Zagazig, Egypt.

出版信息

Noncoding RNA Res. 2021 Feb 13;6(1):35-41. doi: 10.1016/j.ncrna.2021.02.002. eCollection 2021 Mar.

Abstract

PURPOSE

The role of the Sirutin 1 (SIRT1) and MicroRNA-34 a (miR-34a) in endometriosis and the extent to which the miR-34a/SIRT1/p53 signaling pathway is involved in its pathogenesis is unclear, so we aimed to investigate the expression of miRNA 34-a, SIRT1, Forkhead boxO (FoxO-1), p53 and other apoptotic markers in endometrial tissue of women with endometriosis in order to better understand their role and the mechanisms of their actions in the pathogenesis of such disease and if it is related to apoptosis or not.

METHODS

Ectopic and eutopic endometriotic tissues were collected from seventy women with endometriosis while normal endometrial tissues were obtained from 40 fertile women without endometriosis and then gene expression of SIRT-1, miR-34a,p53, Bax, Bcl-2, Bcl-xL and FoxO-1 were measured using RT-PCR.

RESULTS

We detected that SIRT-1 and Bcl-xL genes expressions was significantly up-regulated while miRNA34-a,p53, Bax, Bcl-2 and FoxO-1 were down-regulated in endometrial tissue of endometriotic patients compared to that of those without endometriosis. There was an inverse relationship between SIRT-1a, Bcl-xL genes expressions and miR-34a, p53, Bax, Bcl-2 expressions as well as FoxO-1 expression. These results imply that miR-34a might regulate p53 through SIRT-1 and subsequently FoxO-1 expression in endometriotic tissue, and so it can contribute to the pathogenesis of endometriosis by decreasing the naturally occurring apoptosis in endometrium.

CONCLUSION

This study may provide a potential biomarker for endometriosis therapeutics. Identification of target genes downstream of these transcriptional factors would allow better understanding of their respective roles in the pathogenesis of endometriosis

摘要

目的

沉默调节蛋白1(SIRT1)和微小RNA-34a(miR-34a)在子宫内膜异位症中的作用以及miR-34a/SIRT1/p53信号通路参与其发病机制的程度尚不清楚,因此我们旨在研究miRNA 34-a、SIRT1、叉头框O(FoxO-1)、p53和其他凋亡标志物在子宫内膜异位症女性子宫内膜组织中的表达,以便更好地了解它们在此类疾病发病机制中的作用及其作用机制,以及它是否与细胞凋亡相关。

方法

从70例子宫内膜异位症女性中收集异位和在位子宫内膜组织,同时从40例无子宫内膜异位症且生育能力正常的女性中获取正常子宫内膜组织,然后使用逆转录聚合酶链反应(RT-PCR)检测SIRT-1、miR-34a、p53、Bax、Bcl-2、Bcl-xL和FoxO-1的基因表达。

结果

我们检测到,与无子宫内膜异位症的女性相比,子宫内膜异位症患者子宫内膜组织中SIRT-1和Bcl-xL基因表达显著上调,而miRNA34-a、p53、Bax、Bcl-2和FoxO-1表达下调。SIRT-1a、Bcl-xL基因表达与miR-34a、p53、Bax、Bcl-2表达以及FoxO-1表达之间呈负相关。这些结果表明,miR-34a可能通过SIRT-1调节p53,进而调节子宫内膜异位症组织中FoxO-1的表达,因此它可能通过减少子宫内膜中自然发生的细胞凋亡而促进子宫内膜异位症的发病机制。

结论

本研究可能为子宫内膜异位症治疗提供一种潜在的生物标志物。鉴定这些转录因子下游的靶基因将有助于更好地了解它们在子宫内膜异位症发病机制中的各自作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c7b/7905260/d5d37c6517fe/gr1.jpg

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