The Relationship and Expression of miR-451a, miR-25-3p and PTEN in Early Peritoneal Endometriotic Lesions and Their Modulation In Vitro.

The Relationship and Expression of miR-451a, miR-25-3p and PTEN in Early Peritoneal Endometriotic Lesions and Their Modulation In Vitro.
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DOI:
10.3390/ijms23115862
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发表时间:
2022-05-24
影响因子:
5.6
通讯作者:
Findley, Austin
Findley, Austin
中科院分区:
生物学2区
文献类型:
--
作者:
Nothnick, Warren B.;Peterson, Riley;Minchella, Paige;Falcone, Tommaso;Graham, Amanda;Findley, Austin

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背景:MIR-451a可作为肿瘤抑制因子发挥作用,并已被证明在子宫内膜异位症病变组织和子宫内膜异位症患者血清中均升高。为了进一步探讨miR-451a在子宫内膜异位症的病理生理机制中的作用,特别是进一步评估其与肿瘤抑制因子、磷酸酶和张力蛋白同源物(PTEN)的关系,我们检测了它们在子宫内膜异位症病变组织中的表达,以了解它们之间的关系,并进一步探讨miR-451a是否调节PTEN的表达。方法:收集46例子宫内膜异位症患者的55例红色腹膜异位内膜病变及配对的在位内膜标本。用qRT-PCR检测miR-451a、miR-25-3p和PTEN的mRNA水平,并报告每个匹配的在位和异位样本。为探讨miR-451a和miR-25-3p在子宫内膜异位上皮细胞中的表达,将miR-25-3p和miR-25-3p分别导入子宫内膜异位上皮细胞系12Z细胞,用qRT-PCR法检测miR-25-3p的表达,Western blotting法检测PTEN蛋白的表达。结果:PTEN与miR-25-3p的表达呈负相关,miR-25-3p与miR-451a在单个皮损中的表达呈负相关。在12Z细胞中,miR-451a过表达导致miR-25-3p表达下调,miR-25-3p上调导致PTEN蛋白表达下调。结论:通过对子宫内膜异位病变个体化表达的评估,我们发现miR-451a、miR-25-3p与PTEN的表达呈负相关,而体外细胞转染研究表明miR-451a可能通过调节miR-25-3p来调节PTEN的表达。
Background: miR-451a can function as a tumor suppresser and has been shown to be elevated in both endometriotic lesion tissue and serum from women with endometriosis. To further explore the role of miR-451a in the pathophysiology of endometriosis, specifically, further evaluating its association with the tumor suppressor, phosphatase and tensin homolog (PTEN), we examined their expression in individual endometriotic lesion tissue to gain insight into their relationship and further explore if miR-451a regulates PTEN expression. Methods: A total of 55 red, peritoneal endometriotic lesions and matched eutopic endometrial specimens were obtained from 46 patients with endometriosis. miR-451a, miR-25-3p and PTEN mRNA levels were assessed by qRT-PCR and reported for each matched eutopic and ectopic sample. To evaluate miR-451a and miR-25-3p expression of miR-25-3p and PTEN, respectively, 12Z cells (endometriotic epithelial cell line) were transfected and miR-25-3p expression was assessed by qRT-PCR, while PTEN protein expression was assessed by Western blotting. Results: PTEN and miR-25-3p expression exhibited an inverse relationship, as did miR-25-3p and miR-451a in individual lesions. Over-expression of miR-451a in 12Z cells resulted in down-regulation of miR-25-3p, while up-regulation of miR-25-3p resulted in down-regulation of PTEN protein expression. Conclusions: By assessing individual endometriotic lesion expression, we discovered an inverse relationship between miR-451a, miR-25-3p and PTEN, while in vitro cell transfection studies suggest that miR-451a may regulate PTEN expression via modulating miR-25-3p.
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