Mechanisms of KLF10 in regulating proliferation of endometriotic stromal cells in endometriosis.

Objectives: Endometriotic stromal cells (ESCs) are extensively found in endometriosis (EM). This study aims to investigate the effects and regulatory mechanisms of KLF10 on the proliferation of ESCs in EM.

Methods: Human ESCs from eutopic and ectopic endometrium were isolated and identified. Levels of KLF10, miR-200c-3p, and lncRNA NEAT1 in cells were detected by RT-qPCR and western blot analysis. Expression of KLF10, miR-200c-3p and NEAT1 were silenced in ectopic ESCs, followed by an assessment of cell proliferation. Chromatin immunoprecipitation and dual-luciferase reporter assays were conducted to analyze the binding of KLF10 to the miR-200c-3p promoter. RNA immunoprecipitation and dual-luciferase reporter assays were performed to analyze the interaction between miR-200c-3p and NEAT1. NEAT1 RNA stability was measured.

Results: Compared to Eut-ESCs, Ect-ESCs exhibited decreased KLF10 and miR-200c-3p expression and increased NEAT1 expression. Overexpression of KLF10 inhibited the proliferation of Ect-ESCs. Mechanistically, KLF10 transcriptionally promoted miR-200c-3p expression, reducing the binding of miR-200c-3p to NEAT1 and downregulating NEAT1 expression. Combined experimental results showed that miR-200c-3p downregulation or NEAT1 overexpression could alleviate the inhibitory effect of KLF10 overexpression on the proliferation of Ect-ESCs. Limitations We only investigated the function of KLF10 in Ect-ESC proliferation of EM on the cellular level, but the effect of KLF10 on abnormal Ect-ESC migration and invasion remains to be explored. Besides, there is no interference experiments performed on Eut-ESCs, and no animal experiment was included. Conclusions KLF10 transcriptionally promoted miR-200c-3p expression, reduced the binding of miR-200c-3p to NEAT1, thus downregulating NEAT1 expression and inhibiting the proliferation of Ect-ESCs.