{"doi":"10.1093/nar/gkaf1526","title":"The long noncoding RNA\n                    <i>VIM-AS1</i>\n                    and nucleoporin Nup358/RanBP2 regulate SMAD nuclear accumulation during TGF-β signaling","abstract":"The transforming growth factor β (TGF-β) pathway is a developmental signaling network that regulates tissue homeostasis and malfunctions in human diseases, including cancer. TGF-β signals via two receptors, which activate SMAD and alternative signaling pathways. We show that TGF-β induces the expression of the mammalian long noncoding RNA (lncRNA) VIM-AS1 (Vimentin antisense RNA1) variant-2 (v.2) via a transcriptional SMAD-GATA6-SPI1 complex. VIM-AS1 v.1 and v.2 localize in different cell compartments, including the nuclear border. Unbiased whole transcriptomic analysis and functional gain and loss of function assays establish that VIM-AS1 v.2 enhances TGF-β signaling. Mechanistically, VIM-AS1 v.2 interacts with the nucleoporin Nup358/RanBP2, contributing to the binding of Nup358/RanBP2 to SMAD2/3 and enhancing SMAD nuclear accumulation. In the context of cancer biology, VIM-AS1 did not affect the antiproliferative actions of TGF-β, yet had an impact on the epithelial-mesenchymal transition gene program, and increased the invasion and motility of tumor cells, whereas its silencing sensitized cancer cells to chemotherapeutic agents. The molecular mechanism highlights how a lncRNA can modulate the nuclear pore's capacity to import SMAD complexes, by facilitating their capture by Nup358/RanBP2 and thereby enhancing nuclear accumulation of SMADs with distinct isoform composition, thus promoting selectively TGF-β signaling responses.","journal":"Nucleic Acids Research","year":2026,"id":2673,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0385,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2026-01-14","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":31064,"name":"Mohamad Moustafa Ali","orcid":"0000-0002-4902-0550","position":1,"is_corresponding":false},{"id":31065,"name":"Yuka Itoh","orcid":"0009-0002-0596-4100","position":2,"is_corresponding":false},{"id":31066,"name":"Mafalda Sousa Ferreira","orcid":null,"position":3,"is_corresponding":false},{"id":31067,"name":"Johan Heldin","orcid":"0000-0002-0915-5303","position":4,"is_corresponding":false},{"id":31068,"name":"Hao Fu","orcid":null,"position":5,"is_corresponding":false},{"id":31069,"name":"André Hoelz","orcid":"0000-0003-1726-0127","position":6,"is_corresponding":false},{"id":31070,"name":"Carl-Henrik Heldin","orcid":null,"position":7,"is_corresponding":false},{"id":31071,"name":"Aristidis Moustakas","orcid":"0000-0001-9131-3827","position":8,"is_corresponding":false},{"id":31072,"name":"Mafalda S. Ferreira","orcid":"0000-0002-0238-3522","position":9,"is_corresponding":false},{"id":31073,"name":"Fu Hao","orcid":"0009-0000-3729-5728","position":10,"is_corresponding":false},{"id":31063,"name":"Dorival Mendes Rodrigues-Junior","orcid":"0000-0002-8861-9240","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}