Deciphering the role of hsa-piR-775 in primary ovarian insufficiency through FOXG1 modulation

Primary Ovarian Insufficiency (POI) impacts 3.5% of women under 40, with its etiology largely unknown. Piwi-interacting RNAs (piRNAs) have emerged as potential biomarkers for gynecological conditions, including POI. We hypothesized that hsa-piR-775 plays a critical role in POI pathogenesis by regulating FOXG1 expression.

We performed piRNA sequencing on serum samples from POI patients and controls using the Illumina sequencing platform. Bioinformatics analysis for target prediction was conducted using TargetScan and miRanda to identify potential downstream targets of differentially expressed piRNAs (DEPs). qPCR and luciferase reporter assays for in vitro validation to explore the function and targets of DEPs, with a focus on hsa-piR-775.

Among 43 DEPs, hsa-piR-775 was notably upregulated in POI patients. Target gene prediction and enrichment analysis implicated FOXG1, a gene associated with ovarian function, as a potential target of hsa-piR-775. In vitro validation confirmed hsa-piR-775 can influence FOXG1 mRNA, reducing FOXG1 expression. These findings suggest hsa-piR-775 influences POI progression by modulating FOXG1 levels.

We demonstrate that hsa-piR-775 is upregulated in POI and regulates FOXG1 expression, revealing a novel pathogenic mechanism. This supports piRNAs' potential as biomarkers and therapeutic targets in POI. Future studies should focus on validating these findings in larger cohorts and exploring piRNA-based therapeutic interventions for POI.