ArticleCell communication and signaling : CCS2023
The long non-coding RNA LINC00707 interacts with Smad proteins to regulate TGFβ signaling and cancer cell invasion.
Article in Cell communication and signaling : CCS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
- Expression and mechanistic roles of long non-coding RNAs in diabetic cataract: a systematic review and meta-analysis.Biology direct · 2026Pooled it
- A Transcriptome-Wide Analysis Nominates DIO3OS and C9orf139 as Survival-Associated Long Non-Coding RNAs in Glioblastoma.Non-coding RNA · 2026Article
- circCACNA1D drives pulmonary fibrosis by regulating pyruvate kinase M2 dimer‑tetramer switching.International journal of molecular medicine · 2026Article
- Targeting TGF-β signaling in glioblastoma: therapeutic implications and novel drug development strategies.Brain tumor pathology · 2025Review
- SMAD3 and p300 complex scaffolding by long non-coding RNA LIMD1-AS1 promotes TGF-β-induced breast cancer cell plasticity.Nucleic acids research · 2025Article
- T-Cadherin (International journal of molecular sciences · 2025Review
- Expression Patterns of SMAD1-8 in the Peripheral Facial Nerve Following Compressive Nerve Injury or Axotomy.International journal of molecular sciences · 2025Article
- A prognostic signature of Glutathione metabolism-associated long non-coding RNAs for lung adenocarcinoma with immune microenvironment insights.Frontiers in immunology · 2025Article
- Integrative analysis of m7G methylation-associated genes prognostic signature with immunotherapy and identification of LARP1 as a key oncogene in head and neck squamous cell carcinoma.Frontiers in immunology · 2025Article
- Roles of SMAD and SMAD-Associated Signaling Pathways in Nerve Regeneration Following Peripheral Nerve Injury: A Narrative Literature Review.Current issues in molecular biology · 2024Review
- The TGF-β Family in Glioblastoma.International journal of molecular sciences · 2024Review
- Unboxing the network among long non-coding RNAs and TGF-β signaling in cancer.Upsala journal of medical sciences · 2024Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLong non-coding RNAs (lncRNAs) regulate cellular processes by interacting with RNAs or proteins. Transforming growth factor β (TGFβ) signaling via Smad proteins regulates gene networks that control diverse biological processes, including cancer cell migration. LncRNAs have emerged as TGFβ targets, yet, their mechanism of action and biological role in cancer remain poorly understood.
methodsWhole-genome transcriptomics identified lncRNA genes regulated by TGFβ. 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 TGFβ-regulated lncRNAs was based on new transcriptomics and by combining RNAscope with immunohistochemical analysis in tumor tissue.
resultsTranscriptomics of TGFβ 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 Krüppel-like factor 6 to the LINC00707 promoter, TGFβ led to LINC00707 repression. Functionally, LINC00707 suppressed cancer cell invasion, as well as key fibrogenic and pro-mesenchymal responses to TGFβ, 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 TGFβ 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.
conclusionsLINC00707 interacts with Smad proteins and limits the output of TGFβ signaling, which decreases LINC00707 expression, thus favoring cancer cell invasion. Video Abstract.
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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.