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SKP2 调控 ZEB1 的表达,刺激在位子宫内膜间质细胞侵袭和子宫腺肌病增殖。

SKP2 regulates ZEB1 expression and stimulates eutopic endometrial stromal cell invasion and proliferation of adenomyosis.

机构信息

Department of Gynecology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, China.

Department of Dermatology, Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, China.

出版信息

Reprod Biol. 2022 Mar;22(1):100578. doi: 10.1016/j.repbio.2021.100578. Epub 2021 Nov 26.

Abstract

Though endometriosis is benign, however, it shares certain characteristics with cancers, such as the ability to invade and metastasize. Previous studies have demonstrated that S-phase kinase associated protein2 (SKP2) promotes invasion, tumorigenesis, and metastasis. However, its correlation with adenomyosis is unclear. Herein, we aimed to look into SKP2 expression patterns and regulatory effects on endometrial stromal cell (ESC) proliferation and invasion, and its internal mechanism in adenomyosis. Western blot, qRT-PCR, and immunochemistry were carried out for detecting SKP2 and ZEB1 expression in ESC of adenomyosis and adenomyosis endometrial tissue. The primary ESCs were identified using immunofluorescence. SKP2 knockdown was accomplished in vitro by transfecting a particular lentivirus vector. The colony formation and CCK-8 assays were carried out for assessing cell proliferation, while cell invasion potential was assessed using the transwell assay. Both SKP2 and ZEB1 were found to be significantly upregulated in adenomyosis endometrial tissue. Knockdown of SKP2 inhibited adenomyotic ESC invasion and proliferation. Further experiments showed that knocking out SKP2 reduced ZEB1 expression in adenomyotic ESCs. Our results showed that SKP2 could regulate ZEB1 expression, and increased SKP2 may play a role in the pathogenesis of adenomyosis and stimulating ESC proliferation and invasion.

摘要

虽然子宫内膜异位症是良性的,但它具有某些与癌症相似的特征,例如侵袭和转移的能力。先前的研究表明,S 期激酶相关蛋白 2(SKP2)促进侵袭、肿瘤发生和转移。然而,其与子宫腺肌病的相关性尚不清楚。在此,我们旨在研究 SKP2 在子宫内膜基质细胞(ESC)增殖和侵袭中的表达模式及其对 ESC 的调节作用,以及其在子宫腺肌病中的内在机制。通过 Western blot、qRT-PCR 和免疫组织化学检测子宫腺肌病和子宫腺肌病子宫内膜组织中 SKP2 和 ZEB1 的表达。通过免疫荧光鉴定原代 ESC。通过转染特定的慢病毒载体在体外敲低 SKP2。通过集落形成和 CCK-8 测定评估细胞增殖,通过 Transwell 测定评估细胞侵袭潜能。结果发现,在子宫腺肌病子宫内膜组织中,SKP2 和 ZEB1 的表达均显著上调。敲低 SKP2 抑制了子宫腺肌病 ESC 的侵袭和增殖。进一步的实验表明,敲除 SKP2 降低了子宫腺肌病 ESC 中的 ZEB1 表达。我们的结果表明,SKP2 可以调节 ZEB1 的表达,而 SKP2 的增加可能在子宫腺肌病的发病机制中发挥作用,并刺激 ESC 的增殖和侵袭。

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