Related Experiment Video
Updated: Oct 16, 2025
Author Spotlight: Investigating the Mechanisms and Inducing Models of Polycystic Ovary Syndrome
Published on: July 5, 2024
MiR-let-7d-3p inhibits granulosa cell proliferation by targeting TLR4 in polycystic ovary syndrome
Wei Wu1, Cuicui Duan2, Houyi Lv2
1The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, China.
Abstract:
Polycystic ovary syndrome (PCOS) is a typical reproductive and endocrinological disorder of women at child-bearing age. In this study, we used miRNA sequencing technology and verified miR-let-7d-3p as a vital miRNA in PCOS. RT-qPCR confirmed miR-let-7d-3p was significantly increased in granulosa cells (GCs) of PCOS. Cell counting kit-8 (CCK-8) identified the suppression of miR-let-7d-3p mimic in KGN cell proliferation and PI3K/Akt signaling pathway. Dual luciferase reporter assay proved that Toll-like receptor 4 (TLR4) was a target of miR-let-7d-3p, and TLR4 was significantly down-regulated by miR-let-7d-3p. Furthermore, over-expression of TLR4 promoted KGN cell proliferation and rescued the inhibition of miR-let-7d-3p on KGN cells. In conclusion, miR-let-7d-3p was a crucial miRNA up-regulated in GCs of PCOS, and inhibited cell proliferation by targeting TLR4 gene.
Insights
MicroRNA-let-7d-3p is elevated in polycystic ovary syndrome (PCOS) granulosa cells, inhibiting proliferation by targeting Toll-like receptor 4 (TLR4). This finding offers new insights into PCOS pathogenesis and potential therapeutic targets.
Area of Science:
- Endocrinology
- Molecular Biology
- Reproductive Medicine
Background:
- Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting women of reproductive age.
- Understanding the molecular mechanisms underlying PCOS is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of microRNA (miRNA) in PCOS pathogenesis.
- To identify specific miRNAs and their target genes involved in PCOS development.
Main Methods:
- miRNA sequencing to identify differentially expressed miRNAs in PCOS.
- RT-qPCR to validate miRNA levels in granulosa cells (GCs).
- Cell proliferation assays (CCK-8) and dual luciferase reporter assays to determine gene targets and pathways.
Main Results:
- miR-let-7d-3p was significantly upregulated in GCs from PCOS patients.
- miR-let-7d-3p mimic suppressed KGN cell proliferation and the PI3K/Akt signaling pathway.
- Toll-like receptor 4 (TLR4) was identified as a direct target of miR-let-7d-3p, with its expression downregulated by the miRNA.
- Overexpression of TLR4 rescued the inhibitory effect of miR-let-7d-3p on KGN cell proliferation.
Conclusions:
- miR-let-7d-3p is a key miRNA upregulated in PCOS GCs.
- This miRNA inhibits cell proliferation by targeting the TLR4 gene, suggesting a novel regulatory mechanism in PCOS.
Related Concept Videos
01:22MicroRNAs
01:30Hormonal Control of the Ovarian Cycle
Before puberty, the hypothalamus releases GnRH in a low frequency, low amplitude pulsatile manner. This along with the immature hypothalamic-pituitary-gonadal axis activity, results in low estrogen levels and the absence of a fully functional ovarian cycle. At puberty, GnRH secretion increases in both frequency and...
01:22Hormonal Regulation of the Menstrual Cycle
At puberty, GnRH begins a pulsatile release pattern, which triggers the anterior pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The frequency and amplitude of GnRH pulses vary across the menstrual cycle, with faster pulses favoring LH release and slower pulses favoring FSH...