Inhibition of lysine-specific histone demethylase 1A suppresses adenomyosis through reduction in ectopic endometrial stromal cell proliferation, migration, and invasion

Limei Cui; Changmei Sang; Ruoqing Li; Shuping Zhao

doi:10.25259/Cytojournal_48_2024

Inhibition of lysine-specific histone demethylase 1A suppresses adenomyosis through reduction in ectopic endometrial stromal cell proliferation, migration, and invasion

Cytojournal. 2024 Nov 22:21:50. doi: 10.25259/Cytojournal_48_2024. eCollection 2024.

Authors

Limei Cui^{1

2}, Changmei Sang³, Ruoqing Li⁴, Shuping Zhao¹

Affiliations

¹ Department of Gynecology , Qingdao Women and Children's Hospital, Shandong University, Qingdao, China.
² Department of Gynecology, Qingzhou People's Hospital, Weifang, China.
³ Department of Gynecology, Qingdao Women and Children's Hospital, Qingdao, China.
⁴ Medical College, Qingdao University, Qingdao, Shandong, China.

Abstract

Objective: Deep endometriosis is now referred to as adenomyosis externa, whereas adenomyosis is once known as endometriosis interna. Lysine-specific histone demethylase 1A (KDM1A, commonly LSD1) is a lysine demethylase that targets histone and non-histone proteins. This study aimed to assess how KDM1A affects the migration, invasion, and proliferation of adenomyosis-derived endometrial stromal cells (ESCs).

Material and methods: Immunocytochemistry staining was used to identify primary ectopic endometrial stromal cells (EESCs) and eutopic endometrial stromal cells (EuESCs) were isolated and purified from patients with complete hysterectomy for adenomyosis. Cell counting kit-8 assay, colony formation, wound scratch, and transwell assays were used to investigate the effect of silencing KDM1A on the inhibition cell viability, colony, migration, and invasion, respectively. Mechanistic investigations were carried out by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR).

Results: Vimentin staining was highly positive and cytokeratin staining was nearly negative in EESCs and EuESCs. KDM1A silencing reduced the ability of EESCs and EuESCs to proliferate (P < 0.001). The proliferation, motility, and invasiveness of EESCs and EuESCs were markedly reduced when KDM1A was silenced (P < 0.001). KDM1A silencing substantially downregulated invasion- and migration-related proteins or genes according to Western blot and qRT-PCR analysis (P < 0.05). EESCs and EuESCs with KDM1A silencing showed a higher reduction in these proteins than the control group (P < 0.05).

Conclusion: In adenomyosis, silencing KDM1A can limit the motility, invasiveness, and proliferation of EuESCs and EESCs. These outcomes could potentially correlate with the decreased expression levels of matrix metalloproteinases (MMP)-2, MMP-9, Fascin, and Erzin proteins.

Keywords: adenomyosis; endometrial stromal cells; lysine-specific histone demethylase 1A; metastasis migration; proliferation.

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