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KDM1A 调控组蛋白去乙酰化抑制 DACT1 表达对宫颈癌增殖和迁移的影响。

Histone Deacetylation Regulated by KDM1A to Suppress DACT1 in Proliferation and Migration of Cervical Cancer.

机构信息

No. 3 Obstetrics and Gynecology Department, Hunan Provincial People's Hospital, No. 61, West Jiefang Road, Furong District, Changsha, Hunan 410005, China.

出版信息

Anal Cell Pathol (Amst). 2021 Jul 24;2021:5555452. doi: 10.1155/2021/5555452. eCollection 2021.

DOI:10.1155/2021/5555452
PMID:34350095
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8328692/
Abstract

OBJECTIVE

Increased expression of KDM1A and decreased expression of DACT1 in cervical cancer cells were noticed in a previous study. This study is aimed at exploring the mechanism behind the KDM1A regulation on DACT1 in cervical cancer cells.

METHODS

The expression profile of KDM1A and DACT1 in cervical cancer tissues was searched in TCGA database. In vitro experiments verified the effect of KDM1A and DACT1 on proliferation and migration ability of cervical cancer cell lines after cell transfection. The interaction of KDM1A with HDAC1 was identified by coimmunoprecipitation (Co-IP). The expression levels of KDM1A and DACT1 in cervical cancer cell lines were determined by qRT-PCR and western blot.

RESULTS

TCGA database showed that cervical cancer tissues had elevated expression of KDM1A and decreased expression of DACT1, which was consistent with the observation in cervical cancer cell lines. KDM1A was found to negatively regulate DACT1 through histone deacetylation. Meanwhile, the downregulation of KDM1A or overexpression of DACT1 could suppress the cell proliferation and migration ability in HeLa and SiHa cells. Cotransfection of KDM1A and DACT1 overexpression could reverse the increased cell proliferation and migration ability induced by KDM1A overexpression.

CONCLUSION

KDM1A can downregulate DACT1 expression through histone deacetylation and therefore suppress the proliferation and migration of cervical cancer cells.

摘要

目的

在之前的研究中注意到宫颈癌细胞中 KDM1A 的表达增加和 DACT1 的表达减少。本研究旨在探讨 KDM1A 对宫颈癌细胞中 DACT1 的调节机制。

方法

在 TCGA 数据库中搜索宫颈癌组织中 KDM1A 和 DACT1 的表达谱。通过细胞转染,体外实验验证了 KDM1A 和 DACT1 对宫颈癌细胞系增殖和迁移能力的影响。通过共免疫沉淀(Co-IP)鉴定 KDM1A 与 HDAC1 的相互作用。通过 qRT-PCR 和 Western blot 确定宫颈癌细胞系中 KDM1A 和 DACT1 的表达水平。

结果

TCGA 数据库显示,宫颈癌组织中 KDM1A 的表达升高,DACT1 的表达降低,与宫颈癌细胞系中的观察结果一致。KDM1A 通过组蛋白去乙酰化负调控 DACT1。同时,下调 KDM1A 或过表达 DACT1 可抑制 HeLa 和 SiHa 细胞的增殖和迁移能力。共转染 KDM1A 和 DACT1 过表达可逆转 KDM1A 过表达诱导的细胞增殖和迁移能力增加。

结论

KDM1A 可以通过组蛋白去乙酰化下调 DACT1 的表达,从而抑制宫颈癌细胞的增殖和迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c941/8328692/795add554ee9/ACP2021-5555452.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c941/8328692/95f0bc3c471a/ACP2021-5555452.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c941/8328692/e25f9970c304/ACP2021-5555452.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c941/8328692/877e10267e79/ACP2021-5555452.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c941/8328692/1db39584f9ed/ACP2021-5555452.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c941/8328692/795add554ee9/ACP2021-5555452.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c941/8328692/95f0bc3c471a/ACP2021-5555452.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c941/8328692/e25f9970c304/ACP2021-5555452.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c941/8328692/877e10267e79/ACP2021-5555452.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c941/8328692/1db39584f9ed/ACP2021-5555452.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c941/8328692/795add554ee9/ACP2021-5555452.005.jpg

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