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Cell Signal ; 120: 111230, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38761988

ABSTRACT

Despite decades of research, endometriosis remains a mysterious gynecological disease with unknown etiology and pathogenesis. Krüppel-like Factor 6 (KLF6), a transcription factor, has a wide expression profile and regulates a variety of biological processes. Here, we investigated the expression and function of KLF6 and its possible regulatory mechanisms in endometriosis. To determine the function of KLF6, knockdown and overexpression experiments were performed in eutopic endometrial stromal cells (EU-ESCs) and ectopic endometrial stromal cells (EC-ESCs), respectively. Cell viability, apoptosis, migration, invasion, and angiogenesis assays were conducted in ESCs. ChIP-sequencing and mRNA-sequencing were performed to investigate the functional mechanism of KLF6 in regulating ESCs. We found that KLF6 was highly expressed in eutopic endometrium of endometriosis patients, compared with ectopic endometrium. Similarly, the same was true in EU-ESCs, which was compared with EC-ESCs. Overexpression of KLF6 significantly suppressed EC-ESC proliferation, migration and invasion and induced cell apoptosis, while knockdown of KLF6 resulted in the opposite effects on EU-ESCs. Overexpression of KLF6 significantly inhibited EC-ESC angiogenesis. Mechanistically, the results of ChIP sequencing and mRNA sequencing revealed that CTNNB1 may be a transcriptional target regulated by KLF6. Reintroduction of KLF6 reversed the effects of KLF6 knockdown on EU-ESCs. KLF6 inhibited the proliferation, migration and angiogenesis of EC-ESCs by inhibiting the expression of CTNNB1. Our findings provided a new perspective on the role of KLF6 in endometriosis progression and inspire potential targeted therapeutic strategies.


Subject(s)
Cell Movement , Endometriosis , Endometrium , Kruppel-Like Factor 6 , Stromal Cells , beta Catenin , Humans , Female , Endometriosis/metabolism , Endometriosis/pathology , Endometriosis/genetics , Kruppel-Like Factor 6/metabolism , Kruppel-Like Factor 6/genetics , beta Catenin/metabolism , Stromal Cells/metabolism , Stromal Cells/pathology , Endometrium/metabolism , Endometrium/pathology , Adult , Apoptosis/genetics , Cell Proliferation , Disease Progression
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