{"entity": "publication", "iuid": "82c4e6bece814bc1b522bc31cfd32077", "timestamp": "2026-09-30T23:39:30.165Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/82c4e6bece814bc1b522bc31cfd32077.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/82c4e6bece814bc1b522bc31cfd32077"}}, "title": "The long non-coding RNA LINC00707 interacts with Smad proteins to regulate TGF\u03b2 signaling and cancer cell invasion.", "authors": [{"family": "G\u00e9labert", "given": "Caroline", "initials": "C"}, {"family": "Papoutsoglou", "given": "Panagiotis", "initials": "P"}, {"family": "Gol\u00e1n", "given": "Irene", "initials": "I"}, {"family": "Ahlstr\u00f6m", "given": "Eric", "initials": "E"}, {"family": "Ameur", "given": "Adam", "initials": "A"}, {"family": "Heldin", "given": "Carl-Henrik", "initials": "CH"}, {"family": "Caja", "given": "Laia", "initials": "L"}, {"family": "Moustakas", "given": "Aristidis", "initials": "A"}], "type": "video-audio media", "published": "2023-10-02", "journal": {"title": "Cell Commun. Signal", "issn": "1478-811X", "volume": "21", "issue": "1", "pages": "271", "issn-l": "1478-811X"}, "abstract": "Long non-coding RNAs (lncRNAs) regulate cellular processes by interacting with RNAs or proteins. Transforming growth factor \u03b2 (TGF\u03b2) signaling via Smad proteins regulates gene networks that control diverse biological processes, including cancer cell migration. LncRNAs have emerged as TGF\u03b2 targets, yet, their mechanism of action and biological role in cancer remain poorly understood.\n\nWhole-genome transcriptomics identified lncRNA genes regulated by TGF\u03b2. Protein kinase inhibitors and RNA-silencing, in combination with cDNA cloning, provided loss- and gain-of-function analyses. Cancer cell-based assays coupled to RNA-immunoprecipitation, chromatin isolation by RNA purification and protein screening sought mechanistic evidence. Functional validation of TGF\u03b2-regulated lncRNAs was based on new transcriptomics and by combining RNAscope with immunohistochemical analysis in tumor tissue.\n\nTranscriptomics of TGF\u03b2 signaling responses revealed down-regulation of the predominantly cytoplasmic long intergenic non-protein coding RNA 707 (LINC00707). Expression of LINC00707 required Smad and mitogen-activated protein kinase inputs. By limiting the binding of Kr\u00fcppel-like factor 6 to the LINC00707 promoter, TGF\u03b2 led to LINC00707 repression. Functionally, LINC00707 suppressed cancer cell invasion, as well as key fibrogenic and pro-mesenchymal responses to TGF\u03b2, as also attested by RNA-sequencing analysis. LINC00707 also suppressed Smad-dependent signaling. Mechanistically, LINC00707 interacted with and retained Smad proteins in the cytoplasm. Upon TGF\u03b2 stimulation, LINC00707 dissociated from the Smad complex, which allowed Smad accumulation in the nucleus. In vivo, LINC00707 expression was negatively correlated with Smad2 activation in tumor tissues.\n\nLINC00707 interacts with Smad proteins and limits the output of TGF\u03b2 signaling, which decreases LINC00707 expression, thus favoring cancer cell invasion. Video Abstract.", "doi": "10.1186/s12964-023-01273-3", "pmid": "37784093", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10544626"}, {"db": "pii", "key": "10.1186/s12964-023-01273-3"}], "notes": [], "created": "2026-09-23T11:20:01.994Z", "modified": "2026-09-23T11:20:02.021Z"}