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Updated: Jan 19, 2026
Author Spotlight: Investigating the Mechanisms and Inducing Models of Polycystic Ovary Syndrome
Published on: July 5, 2024
MicroRNA-486-5p inhibits ovarian granulosa cell proliferation and participates in the development of PCOS via
1Reproductive Health Division, Zoucheng Maternal and Child Health and Family Planning Service Center, Zoucheng, China. yszjl0156@tom.com.
Objective:
To explore whether microRNA-486-5p affected the proliferation of ovarian granulosa cells by targeting MST4 (silk/threonine protein kinase 4), thereby promoting the development of polycystic ovary syndrome (PCOS).
Materials And Methods:
The level of microRNA-486-5p in PCOS tissues and adjacent normal tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). After microRNA-486-5p up-regulation in KNG cells, the mRNA and protein level of related genes was examined using qRT-PCR and western blot assay, respectively. Meanwhile, cell proliferation and cell cycle were analyzed by cell counting kit-8 (CCK-8) assay and flow cytometry. After insulin treatment of KNG cells, expressions of microRNA-486-5p and MST4, cell proliferation as well as cell cycle, were detected by qRT-PCR, CCK-8 and flow cytometry, respectively. Furthermore, cell proliferation and cycle situation were examined after simultaneous up-regulation of MST4 and microRNA-486-5p in vitro.
Results:
MicroRNA-486-5p expression in PCOS tissues was significantly lower than that of normal tissues. In KNG cells, up-regulation of microRNA-486-5p significantly inhibited cell proliferation and cell cycle. The levels of cycle-associated proteins including CDK2 and CCNB1 decreased significantly. The results of dual-luciferase reporter gene assay showed that microRNA-486-5p could bind to MST4. After up-regulating microRNA-486-5p, both the mRNA and protein levels of MST4 decreased remarkably. MST4 expression was found significantly elevated in PCOS tissues as well. After overexpression of MST4, cell proliferation was enhanced, cell cycle was promoted, and expressions of cycle-related proteins increased. After treatment with different concentrations of insulin in KNG cells, the expression level of microRNA-486-5p decreased in a concentration-dependent manner. However, opposite results were observed in MST4 level. Meanwhile, the proliferation ability and cell cycle of insulin-treated cells were significantly enhanced. In addition, the inhibitory effect of microRNA-486-5p on cell proliferation and cell cycle could be partially reversed by simultaneous up-regulation of MST4 and microRNA-486-5p.
Conclusions:
MicroRNA-486-5p can bind to MST4 in a targeted manner and inhibit the proliferation of ovarian granulosa cells, thereby inhibiting the development of PCOS.
Insights
MicroRNA-486-5p inhibits ovarian granulosa cell proliferation by targeting MST4, offering a potential therapeutic strategy for polycystic ovary syndrome (PCOS). This microRNA is downregulated in PCOS, and its restoration may counteract disease progression.
Area of Science:
- Molecular Biology
- Endocrinology
- Genetics
Background:
- Polycystic ovary syndrome (PCOS) is a complex endocrine disorder characterized by ovarian dysfunction.
- Ovarian granulosa cells play a crucial role in follicular development and are implicated in PCOS pathogenesis.
- MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and are involved in various cellular processes.
Purpose of the Study:
- To investigate the role of microRNA-486-5p in the proliferation of ovarian granulosa cells.
- To determine if microRNA-486-5p targets MST4 (serine/threonine protein kinase 4) in ovarian granulosa cells.
- To explore the potential of microRNA-486-5p as a therapeutic target for PCOS development.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) to measure microRNA-486-5p and MST4 levels in PCOS and normal tissues.
- Cell culture experiments involving KNG cells with microRNA-486-5p and MST4 manipulation.
- Cell proliferation assays (CCK-8) and flow cytometry to analyze cell cycle progression.
- Dual-luciferase reporter gene assay to confirm the binding of microRNA-486-5p to MST4.
Main Results:
- MicroRNA-486-5p expression was significantly lower in PCOS tissues compared to normal tissues.
- Upregulation of microRNA-486-5p inhibited KNG cell proliferation and cell cycle progression, decreasing CDK2 and CCNB1 levels.
- MicroRNA-486-5p directly targets MST4, leading to decreased MST4 mRNA and protein levels. MST4 was elevated in PCOS tissues.
- Overexpression of MST4 promoted cell proliferation and cell cycle, while insulin treatment in KNG cells decreased microRNA-486-5p and increased MST4.
- Simultaneous upregulation of MST4 partially reversed the inhibitory effects of microRNA-486-5p.
Conclusions:
- MicroRNA-486-5p directly binds to MST4 and inhibits ovarian granulosa cell proliferation.
- The microRNA-486-5p/MST4 axis plays a significant role in the pathogenesis of PCOS.
- Restoring microRNA-486-5p levels may represent a novel therapeutic strategy for PCOS.
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