366: BRCA1P1 suppresses antiviral and antitumor immunity

Han YJ et al., Proceedings of the National Academy of Sciences (PNAS) - This episode examines a PNAS study showing that the BRCA1 pseudogene BRCA1P1 produces circular RNAs that suppress antiviral innate immunity in human cancers; depleting BRCA1P1 activates interferon-stimulated genes, increases apoptosis and chemosensitivity, and enhances immune clearance in preclinical models. Key terms: BRCA1P1, pseudogene, circular RNA, antiviral immunity, breast cancer.

Study Highlights:
BRCA1P1 is expressed broadly across human cancer cell lines and is elevated in breast tumors. The majority of BRCA1P1 transcripts are circular RNAs that bind the NF-κB subunit RelA to attenuate NF-κB–driven antiviral gene transcription. Loss of BRCA1P1 by ASO or CRISPR induces ISGs, IFNβ and TNF, increases apoptosis and sensitivity to chemotherapy, and enhances macrophage phagocytosis. In patient-derived organoids and humanized mouse xenografts BRCA1P1 depletion reduces tumor viability and increases T cell and M1 macrophage infiltration.

Conclusion:
BRCA1P1-derived circular RNAs act as immunosuppressive regulators of antiviral and antitumor immunity in human cancers, and targeting BRCA1P1 activates antiviral programs that reduce tumor growth and boost immune infiltration.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
Regulation of antiviral and antitumor immunity by the BRCA1 pseudogene in human cancers

First author:
Han YJ

Journal:
Proceedings of the National Academy of Sciences (PNAS)

DOI:
10.1073/pnas.2528911123

Reference:
Han YJ, Zhang J, Shariff M, Wu S, Khramtsova G, Nguyen LC, Peiffer DS, Li N, Lewicka A, Moore M, Piccirilli JA, Olopade OI. Regulation of antiviral and antitumor immunity by the BRCA1 pseudogene in human cancers. Proc Natl Acad Sci U S A. 2026;123(19):e2528911123. doi:10.1073/pnas.2528911123

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

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Episode link: https://basebybase.com/episodes/brca1p1-pseudogene-antiviral-immunity

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-05-15.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited the transcript sections describing BRCA1P1 background, circular RNA nature, RelA/NF-κB interaction, depletion experiments (ASO/CRISPR), pancancer expression, antiviral gene upregulation, apoptosis, chemotherapy sensitivity, immune infiltration, PDOs, and humanized mouse models, plus clinical implications and de
- transcript topics: BRCA1P1 background and primate-specificity; BRCA1P1 circular RNA and RelA/NF-κB interaction; BRCA1P1 depletion methods (ASO, CRISPR) and pancancer scope; Antiviral gene induction and cytokine responses; Apoptosis and chemotherapy sensitivity after BRCA1P1 loss; Macrophage phagocytosis and T cell infiltration

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 7
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- BRCA1P1 is a primate-specific, chimeric BRCA1/RPLP1 pseudogene; majority of BRCA1P1 transcripts are circular RNAs (~70-80%).
- BRC...