Evidence map›Paper›PMID 41781465›Full record

ArticleScientific reports2026

Paradoxical oncogenic effects of hepatic Brca1 through modulating Bhmt.

Martha Ghebreselassie, Yoo Jin Park, Diana Nakib, David Dodington, Parasvi Patel, Sohyun Won, Anne Hakem, Razqallah Hakem, Sonya MacParland, Minna Woo

Abstract read
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In one paragraph

Article in Scientific reports, 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

10 authors.

Martha GhebreselassieDepartment of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
Yoo Jin ParkUniversity Health Network Research Institute, University Health Network, Toronto, ON, Canada.
Diana NakibUniversity Health Network Research Institute, University Health Network, Toronto, ON, Canada.
David DodingtonLaboratory Medicine Program, University Health Network, Toronto, Canada.
Parasvi PatelDepartment of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Sohyun WonDepartment of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
Anne HakemPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Razqallah HakemDepartment of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Sonya MacParlandUniversity Health Network Research Institute, University Health Network, Toronto, ON, Canada.
Minna WooDepartment of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. minna.woo@uhn.ca.

Funding

Cancer Research Society 1281091CIHR PJT-195673
6 · The paper itself

Abstract

The well-established tumor suppressor, Breast Cancer Susceptibility Gene 1 (BRCA1), has been implicated in lipid metabolism and in paradoxically promoting hepatocellular carcinoma (HCC); yet its mechanistic role remains unknown. Here we show murine hepatic Brca1 loss protected against fatty liver, glucose intolerance and tumor development. Using single nuclear RNA sequencing, we found betaine-homocysteine S-methyltransferase (Bhmt) was suppressed with Brca1-deficiency. Concomitant knockdown of BRCA1 and BHMT in human hepatoma cells revealed additive accumulation of DNA double strand breaks and increased susceptibility to cell death. In our mouse model and human hepatoma cells, BHMT repression with BRCA1-deficiency was associated with downregulation of choline metabolism, an emerging hallmark of cancer. Metabolomics in hepatic Brca1-deficient mice further revealed related disruptions in choline metabolism. Together, our data show hepatic Brca1-deficiency protected against tumor formation by inducing cell death through exacerbating DNA damage and suppressing choline metabolism by inhibiting Bhmt expression, challenging the role of BRCA1 solely as a tumor suppressor.

Indexed as

BRCA1 ProteinCarcinoma, HepatocellularLiverLiver NeoplasmsAnimalsCell Line, TumorCholineDNA DamageFatty LiverFemaleHumansMiceMice, KnockoutBRCA1 ProteinCholine

Identifiers

PMID41781465
PMCPMC13111711

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LicenceCC BY-NC-ND
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Registered trials

None linked

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 OpenQuestion graph.