LncRNA PKD1P6 modulates ovarian granulosa cell survival of hyperandrogenic polycystic ovary syndrome by targeting miR-135b-5p and inhibiting ERK1/2 signaling
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View abstract on PubMed
Summary
This summary is machine-generated.Polycystic ovary syndrome (PCOS) involves abnormal egg development. This study identifies a long noncoding RNA, PKD1P6, as crucial for regulating ovarian cell function and potentially treating hyperandrogenic PCOS.
Area Of Science
- Endocrinology
- Molecular Biology
- Genetics
Background
- Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age.
- Aberrant folliculogenesis is a hallmark of PCOS, yet its molecular underpinnings are not fully understood.
- Long noncoding RNAs (lncRNAs) are increasingly implicated in PCOS pathogenesis.
Purpose Of The Study
- To investigate the role of lncRNA PKD1P6 in the pathogenesis of hyperandrogenic PCOS (HA-PCOS).
- To elucidate the molecular mechanism by which PKD1P6 influences ovarian granulosa cell function.
- To explore PKD1P6 as a potential therapeutic target for HA-PCOS.
Main Methods
- Quantitative analysis of lncRNA PKD1P6 expression in granulosa cells from HA-PCOS patients.
- In vitro experiments involving overexpression of PKD1P6 and its effects on KGN cell viability, cell cycle, and apoptosis.
- Investigation of exosomal PKD1P6 function.
- Mechanistic studies using RNA immunoprecipitation and Western blotting to assess interactions between PKD1P6, miR-135b-5p, and ERK1/2 signaling.
- In vitro and in vivo PCOS models to evaluate the impact of androgens on PKD1P6 and miR-135b-5p expression.
Main Results
- lncRNA PKD1P6 was significantly downregulated in granulosa cells of HA-PCOS patients and correlated negatively with testosterone levels.
- PKD1P6 overexpression reduced KGN cell viability, DNA synthesis, and promoted apoptosis, while arresting the cell cycle.
- Exosomes from PKD1P6-overexpressing cells mimicked these effects.
- PKD1P6 functions as a competing endogenous RNA (ceRNA) for miR-135b-5p, suppressing ERK1/2 activation.
- Androgens downregulated PKD1P6 and upregulated miR-135b-5p in PCOS models.
Conclusions
- lncRNA PKD1P6 plays a critical role in regulating ovarian granulosa cell function and is clinically significant in HA-PCOS.
- The PKD1P6/miR-135b-5p/ERK1/2 axis represents a novel regulatory mechanism in PCOS-related abnormal folliculogenesis.
- PKD1P6 emerges as a promising therapeutic target for HA-PCOS.
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