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NUCKS1 表达增加在子宫内膜异位症中的作用。

Roles of increased NUCKS1 expression in endometriosis.

机构信息

Hainan Women and Children's Medical Center, Hainan, China.

Key Laboratory of Biochemistry and Molecular Biology, Hainan Medical University, Hainan, China.

出版信息

BMC Womens Health. 2023 Aug 15;23(1):432. doi: 10.1186/s12905-023-02563-1.

DOI:10.1186/s12905-023-02563-1
PMID:37582772
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10426139/
Abstract

BACKGROUND

Endometriosis is still a difficult problem for women. The Nuclear Ubiquitous Casein and cyclin-dependent Kinase Substrate 1 (NUCKS1) gene is located on human chromosome 1q32.1. It encodes the NUCKS1 protein, a 27 kDa nuclear DNA binding protein that plays an important role in cell growth and proliferation. NUCKS1 plays an important role in the development of many diseases. However, its role in endometriosis is unclear.

METHODS

Ectopic endometrial tissues and normal tissue specimens were collected, and the expression of NUCKS1, NF-κB and PI3K was detected by RT-qPCR and immunohistochemistry. Inhibition of NUCKS1 in hEM15A cells, study the changes in cell viability, apoptosis, migration and protein expression by CCK8 assay, flow cytometry, wound-healing assay, western blot and ELISA techniques. The comparison of differences between the two groups was implemented using unpaired sample t test or Mann-whitney U test. One-way analysis of variance or Kruskal-wallis test was used for comparisons among the three groups.

RESULTS

(1) NUCKS1 is highly expressed in endometriosis tissues. (2) Inhibition of NUCKS1 decreases cell viability and capability of migration, and increases apoptosis in endometriosis cells. (3) Expressions of NF-κB and PI3K are increased in endometriosis tissues, and inhibition of NUCKS1 decreases the expression levels of PI3K and NF-κB in endometriosis cells. (4) Inhibition of NUCKS1 decreases the expression of VEGF.

CONCLUSION

(1) NUCKS1 is overexpressed in endometriosis, and inhibition of NUCKS1 inhibits cell viability and capability of migration, and increases apoptosis. (2) NUCKS1 promotes the progress of endometriosis through activating PI3K and NF-κB pathways, and VEFG is also involved in this process.

摘要

背景

子宫内膜异位症仍是女性面临的难题。核普遍存在的钙结合蛋白和细胞周期蛋白依赖性激酶底物 1(NUCKS1)基因位于人类染色体 1q32.1。它编码 NUCKS1 蛋白,一种 27kDa 的核 DNA 结合蛋白,在细胞生长和增殖中发挥重要作用。NUCKS1 在许多疾病的发展中发挥着重要作用。然而,其在子宫内膜异位症中的作用尚不清楚。

方法

收集异位子宫内膜组织和正常组织标本,通过 RT-qPCR 和免疫组织化学检测 NUCKS1、NF-κB 和 PI3K 的表达。在 hEM15A 细胞中抑制 NUCKS1,通过 CCK8 检测、流式细胞术、划痕愈合试验、western blot 和 ELISA 技术研究细胞活力、凋亡、迁移和蛋白表达的变化。采用配对样本 t 检验或 Mann-Whitney U 检验比较两组间差异。采用单因素方差分析或 Kruskal-Wallis 检验比较三组间差异。

结果

(1)NUCKS1 在子宫内膜异位症组织中高表达。(2)抑制 NUCKS1 可降低子宫内膜异位症细胞的活力和迁移能力,并增加其凋亡。(3)NF-κB 和 PI3K 在子宫内膜异位症组织中表达增加,抑制 NUCKS1 可降低子宫内膜异位症细胞中 PI3K 和 NF-κB 的表达水平。(4)抑制 NUCKS1 可降低 VEGF 的表达。

结论

(1)NUCKS1 在子宫内膜异位症中过度表达,抑制 NUCKS1 可抑制细胞活力和迁移能力,并增加凋亡。(2)NUCKS1 通过激活 PI3K 和 NF-κB 通路促进子宫内膜异位症的进展,VEGF 也参与了这一过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43db/10426139/472c5c877c8c/12905_2023_2563_Fig13_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43db/10426139/087007d856de/12905_2023_2563_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43db/10426139/c3731ae54579/12905_2023_2563_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43db/10426139/18409f61a892/12905_2023_2563_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43db/10426139/3a5a5a5b8fb5/12905_2023_2563_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43db/10426139/3b0397c9f63f/12905_2023_2563_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43db/10426139/0c7ecd29ae4d/12905_2023_2563_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43db/10426139/c890d4fc9b24/12905_2023_2563_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43db/10426139/5f700546f53f/12905_2023_2563_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43db/10426139/2dbe805d0aa7/12905_2023_2563_Fig12_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43db/10426139/472c5c877c8c/12905_2023_2563_Fig13_HTML.jpg

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