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A proteogenomic RNA processing mechanism drives sex differences in meningioma
David Raleigh1, Martha Cady2, Ayush Aggarwal1
1University of California San Francisco.
Research Square
|June 12, 2026
Summary
Sex hormones influence meningioma growth by regulating RNA processing proteins. Progestins and testosterone interact with PGRMC1, affecting FXR1 and RBM39 to control progesterone receptor expression and tumor progression.
Area of Science:
- Neuro-oncology
- Endocrinology
- Molecular Biology
Background:
- Meningiomas are the most common primary brain tumors, disproportionately affecting females.
- Progestin hormonal therapies and pregnancy are linked to meningioma risk and regression.
- The molecular mechanisms driving sex differences in meningiomas remain unclear.
Purpose of the Study:
- To investigate the role of sex hormone signaling in meningioma development and sex differences.
- To identify key molecular players regulating meningioma growth and sex-specific behavior.
Main Methods:
- Proteomic analysis of 703 human and canine meningioma and meningeal samples.
- Investigated interactions between PGRMC1, FXR1, and RBM39 in response to sex hormones.
- Analyzed the impact of these interactions on progesterone receptor (PR) expression and downstream gene activation.
Main Results:
- Meningiomas are enriched in RNA processing proteins (FXR1, RBM39) in humans and dogs.
- Sex hormone interactions with PGRMC1 modulate FXR1 and RBM39 activity.
- Progestins inhibit, while testosterone stabilizes, PGRMC1 interactions, influencing PR transcript stabilization and tumor growth genes.
Conclusions:
- Sex hormone interactions with PGRMC1, FXR1, and RBM39 drive meningioma sex differences.
- An estrogen receptor-independent pathway for PR expression is identified.
- Findings suggest potential therapeutic strategies targeting PR and RNA processing pathways.
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