Evidence mapPaperPMID 42282014Full record

ArticleResearch square2026

A proteogenomic RNA processing mechanism drives sex differences in meningioma.

David Raleigh, Martha Cady, Ayush Aggarwal, Nicholas Stevers, Naomi Zakimi, Isabelle Liu, Kanish Mirchia, John Coukos, Pornparn Kongpracha, Yuan Zhou and 25 more

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In one paragraph

Article in Research square, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

35 authors.

David RaleighUniversity of California San Francisco.ORCID 0000-0001-9299-8864
Martha CadyUniversity of California, San Francisco.
Ayush AggarwalUniversity of California San Francisco.
Nicholas SteversUniversity of California San Francisco.
Naomi ZakimiUniversity of California San Francisco.
Isabelle LiuUniversity of California, San Francisco.ORCID 0009-0009-7871-2722
Kanish MirchiaUniversity of California San Francisco.
John CoukosUniversity of California San Francisco.
Pornparn KongprachaUniversity of California San Francisco.
Yuan ZhouUniversity of California San Francisco.
Minh NguyenUniversity of California San Francisco.
Brooke BramanUniversity of California San Francisco.
Nathan LeclairMemorial Sloan Kettering Cancer Center.ORCID 0000-0002-0401-2549
Joanna PhillipsUCSF.ORCID 0000-0002-3789-8120
Kingsley ChowUniversity of California San Francisco.
Siddarth Shamdasani-SenUniversity of California San Francisco.ORCID 0009-0008-7814-2136
Nefeli ChantoustiUniversity of California San Francisco.
Bennedict ChoiUniversity of California San Francisco.
Chibo HongUCSF.
Ryan ToedebuschUniversity of California Davis.
Ryan EnglanderThe Jackson Laboratory for Genomic Medicine.
Julia FrankusUniversity of California San Francisco.
Diya SinhaUniversity of California San Francisco.
Heather KarnerUniversity of California San Francisco.
Jennifer RosenbluthUCSF.
Laura Van T VeerUCSF.ORCID 0000-0002-9838-8298
S John LiuUniversity of California San Francisco.ORCID 0000-0003-1042-0191
Nevan KroganUniversity of California San Francisco.ORCID 0000-0003-4902-337X
Joseph CostelloUniversity of California, San Francisco.ORCID 0000-0003-3189-584X
Olga AnczukówTHE JACKSON LABORATORY FOR GENOMIC MEDICINE.ORCID 0000-0003-0516-2677
Christine ToedebuschUniversity of California Davis.
Pete DickinsonUC Davis School of Veterinary Medicine.
Danielle SwaneyUniversity of California, San Francisco.ORCID 0000-0001-6119-6084

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Meningiomas are the most common primary intracranial tumors and the only brain tumors that are more common in females compared with males1. Progestin hormonal therapies increase the risk of meningioma, and progestin-induced or pregnancy-associated meningiomas can regress as serum progestogen levels normalize2. The mechanisms that underlie sex differences and progestogen signaling in meningioma are unknown. Here we show that sex hormone interaction with PGRMC1, a transmembrane progesterone binding protein, regulates the activity of RNA processing proteins FXR1 and RBM39 to drive meningioma sex differences. The genomic architecture and stem cells underlying meningiomas are conserved across vertebrate species3-5 and, using mass spectrometry-based proteomics to analyze 703 meningioma and meningeal samples, we demonstrate that meningiomas are enriched in RNA processing proteins in humans and dogs. Interactions between PGRMC1, FXR1, and RBM39 are inhibited by progestogens and stabilized by testosterone. After release from PGRMC1, FXR1 and RBM39 bind and stabilize progesterone receptor (PR) transcript to enable expression of PR protein, which induces cell cycle, membrane, and cytoskeleton remodeling genes that drive tumor growth. These findings reveal therapeutic strategies and a PR target gene biomarker that may improve outcomes for patients. More broadly, we elucidate an estrogen receptor-independent mechanism of PR expression that underlies sex differences in cancer.

Identifiers

PMID42282014
PMCPMC13252561

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.