{"entity": "publication", "iuid": "6a109262db7c4af2a9fb7f3abf610950", "timestamp": "2026-09-26T01:02:28.640Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/6a109262db7c4af2a9fb7f3abf610950.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/6a109262db7c4af2a9fb7f3abf610950"}}, "title": "SMAD3 and p300 complex scaffolding by long non-coding RNA LIMD1-AS1 promotes TGF-\u03b2-induced breast cancer cell plasticity.", "authors": [{"family": "Fan", "given": "Chuannan", "initials": "C", "orcid": "0000-0001-8754-4913", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3883a7dff51e4a8e9cb677ccd8c4857e.json"}}, {"family": "Cats", "given": "Davy", "initials": "D", "orcid": "0000-0001-9684-220X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/24e0936de4a94d2897a553394a72b46c.json"}}, {"family": "Selle", "given": "Miriam", "initials": "M"}, {"family": "Khorosjutina", "given": "Olga", "initials": "O"}, {"family": "Dhanjal", "given": "Soniya", "initials": "S"}, {"family": "Schmierer", "given": "Bernhard", "initials": "B"}, {"family": "Mei", "given": "Hailiang", "initials": "H", "orcid": "0000-0003-1781-5508", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f1ca37a4d01943a4a0c1a8c4b385fa53.json"}}, {"family": "Ten Dijke", "given": "Peter", "initials": "P", "orcid": "0000-0002-7234-342X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2193ff2b5f924395ac6d4a9ddd53f20e.json"}}, {"family": "Wang", "given": "Qian", "initials": "Q"}], "type": "journal article", "published": "2025-08-27", "journal": {"title": "Nucleic Acids Res.", "issn": "1362-4962", "volume": "53", "issue": "16", "issn-l": "0305-1048"}, "abstract": "Transforming growth factor (TGF)-\u03b2 signaling enhances cancer cell plasticity by inducing epithelial-to-mesenchymal transition (EMT). Here, we identified a TGF-\u03b2-induced long non-coding RNA, LIMD1 Antisense RNA 1 (LIMD1-AS1) that strengthens the SMAD-mediated transcriptional response to TGF-\u03b2. LIMD1-AS1 expression is upregulated in breast cancer tissues compared to normal breast tissues, and high LIMD1-AS1 expression is associated with poor prognosis in breast cancer patients. Depletion of LIMD1-AS1 hinders TGF-\u03b2-induced EMT, migration, and extravasation of breast cancer cells. Mechanistically, LIMD1-AS1 promotes the interaction between SMAD3 and its transcriptional coactivator p300, thereby enhancing SMAD3 transcriptional activity and TGF-\u03b2/SMAD signaling. We demonstrated that LIMD1-AS1 binds to the MAD homology 2 (MH2) domain of SMAD3 and the interferon-binding domain (IBiD) of p300. Displacing LIMD1-AS1 from p300 by its competitor interferon regulatory factor 3 (IRF3) suppressed the effects of LIMD1-AS1 on potentiating TGF-\u03b2/SMAD signaling. Furthermore, blockage of p300 acetyltransferase activity with a pharmacological inhibitor A-485 reduced the ability of LIMD1-AS1 to enhance SMAD3 transcriptional activity, TGF-\u03b2-induced EMT, and migration. This study identifies LIMD1-AS1 as a novel stimulator of TGF-\u03b2 signaling by establishing a positive feedback loop and highlights its potential as a therapeutic target for breast cancer.", "doi": "10.1093/nar/gkaf841", "pmid": "40889156", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12400928"}, {"db": "pii", "key": "8245226"}], "notes": [], "created": "2026-09-23T12:31:12.159Z", "modified": "2026-09-23T12:31:12.287Z"}