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.