Follicular fluid-derived exosomal miR-143-3p/miR-155-5p regulate follicular dysplasia by modulating glycolysis in granulosa cells in polycystic ovary syndrome

Abstract

Objective Polycystic ovary syndrome (PCOS) is characterized by follicular dysplasia. An insufficient glycolysis-derived energy supply of granulosa cells (GCs) is an important cause of follicular dysplasia in PCOS. Follicular fluid (FF) exosomal microRNAs (miRNAs) have been proven to regulate the function of GCs. In this study, exosomes extracted from clinical FF samples were used for transcriptome sequencing (RNA-seq) analysis, and a human ovarian granulocyte tumour cell line (KGN cells) was used for in vitro mechanistic studies. Methods and results In FF exosomal RNA-seq analysis, a decrease in glycolysis-related pathways was identified as an important feature of the PCOS group, and the differentially expressed miR-143-3p and miR-155-5p may be regulatory factors of glycolysis. By determining the effects of miR-143-3p and miR-155-5p on hexokinase (HK) 2, pyruvate kinase muscle isozyme M2 (PKM2), lactate dehydrogenase A (LDHA), pyruvate, lactate and apoptosis in KGN cells, we found that upregulated miR-143-3p expression in exosomes from the PCOS group inhibited glycolysis in KGN cells; knockdown of miR-143-3p significantly alleviated the decrease in glycolysis in KGN cells in PCOS. MiR-155-5p silencing attenuated glycolytic activation in KGN cells; overexpression of miR-155-5p significantly promoted glycolysis in KGN cells in PCOS. In this study, HK2 was found to be the mediator of miR-143-3p and miR-155-5p in FF-derived exosome-mediated regulation of glycolysis in KGN cells. Reduced glycolysis accelerated apoptosis of KGN cells, which mediated follicular dysplasia through ATP, lactate and apoptotic pathways. Conclusions In conclusion, these results indicate that miR-143-3p and miR-155-5p in FF-derived exosomes antagonistically regulate glycolytic-mediated follicular dysplasia of GCs in PCOS.

Correction: Follicular fluid-derived exosomal miR-143-3p/miR-155-5p regulate follicular dysplasia by modulating glycolysis in granulosa cells in polycystic ovary syndrome

“…Following publication of the original article [ 1 ], the authors identified an omission in the Funding section. The funding section should read as follows:…”

“…Author details 1 Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin 541199, China.…”

Plasma exosomes and contained MiRNAs affect the reproductive phenotype in polycystic ovary syndrome

“…8 Several studies reported many differentially expressed miRNAs in exosomes of follicular fluid of PCOS women, which can promote granulosa cell apoptosis and follicular dysplasia. [9][10][11][12] PCOS, as a systemic disease, compromises many organs, not merely the ovaries. Che X et al found miR-27a-5p in serum exosomes was upregulated and affected TGF-β signaling pathways leading to increased risk of endometrial cancer in PCOS patients.…”

MiR-19b-3p inhibits cell viability and proliferation and promotes apoptosis by targeting IGF1 in KGN cells

“…In this study, we aimed to investigate the functional changes of CCs in EM-associated infertility patients, however, it is di cult to obtain primary human CCs in a sizable amount and culture many generations in vitro. Human granulosa-like tumor cell line KGN maintains the physiological characteristics of normal GCs and well grows many times of passages in culture (12), and KGN cells have been extensively used to study the function and regulatory mechanism of biological factors of GCs (13)(14)(15). Therefore, KGN cells were used for further functional and mechanistic studies.…”