Abstract
Polycystic ovary syndrome (PCOS), characterized by the androgen excess and arrest
of antral follicles, is a common endocrine disorder among women lacking specific diagnostic
biomarkers and therapeutic targets. Herein, we studied the molecular mechanism of
miR-96-5p in the process of PCOS and its potential applications in PCOS. Clinically,
we found that miR-96-5p significantly decreased in serum, follicular fluid and primary
human granulosa cells (hGCs) of PCOS patients (n = 70) vs non-PCOS women (n = 60),
as well as in the ovaries of 3-types of induced PCOS-like mice. Furthermore, we demonstrated
that the elevated circulating miR-96-5p levels were significantly correlated with
the PCOS disordered endocrine clinical features, and the area under the curve of receiver
operating characteristic was 0.8344, with 75.71% specificity and 80% sensitivity.
Mechanically, we identified miR-96-5p as an androgen-regulated miRNA that directly
targets the forkhead transcription factor FOXO1. Inhibition of miR-96-5p decreased
estrogen synthesis, while decreasing the cell proliferation index of KGN via regulating
the expression of FOXO1 and its downstream genes. Inversely, inhibition of FOXO1 abrogated
the effect of miR-96-5p on estrogen synthesis and proliferation index. Of note, ovarian
intra-bursal injection of miR-96-5p agomir rescued the phenotypes of dehydroepiandrosterone-induced
PCOS like mice. In conclusion, our results clarified a vital role of miR-96-5p in
the pathogenesis of PCOS and might serve as a novel diagnostic biomarker and therapeutic
target for PCOS.
Keywords
Abbreviations:
AMH (anti-Mullerian hormone), AR (androgen receptor), AREs (androgen response elements), AUC (area under the curve), BMI (body mass index), CMC (carboxymethylcellulose), CI (confidence interval), DHEA (dehydroepiandrosterone), DHT (dihydrotestosterone), E2 (estradiol), FF (follicular fluid), FSH (follicle-stimulating hormone), FT3 (free triiodothyronine), FT4 (free thyroxine), hGCs (human granulosa cells), INS (insulin), IVF (in-vitro fertilization), LH (luteinizing hormone), mGCs (mouse granulosa cells), miRNAs (microRNAs), MMP (mitochondrial membrane potential), NC (negative control), P (progesterone), PCOS (polycystic ovary syndrome), PI (propidium iodide), PNA (prenatal androgen treatment), PRL (prolactin), qPCR (quantitative real-time PCR), RBP (RNA-binding protein), ROC (receiver operating characteristic), T (testosterone), TSH (thyroid stimulating hormone), TFs (transcription factors), UTR (untranslated region)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: December 28, 2022
Accepted:
December 21,
2022
Received in revised form:
December 19,
2022
Received:
November 2,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 Elsevier Inc. All rights reserved.
