ArticleJournal of hematology & oncology2022
Super-enhancer hijacking LINC01977 promotes malignancy of early-stage lung adenocarcinoma addicted to the canonical TGF-β/SMAD3 pathway.
Article in Journal of hematology & oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- Identification of lncRNAs Deregulated in Epithelial Ovarian Cancer Based on a Gene Expression Profiling Meta-Analysis.International journal of molecular sciences · 2023Pooled it
- A Non-Canonical Core Transcriptional Regulatory Circuit Orchestrates Chromatin Reprogramming to Drive Osimertinib Resistance in Non-Small Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- H2AC19 promotes lung adenocarcinoma progressionActa pharmaceutica Sinica. B · 2026Article
- Super-enhancer-driven LncRNA MIR205HG promotes esophageal squamous cell carcinoma progression via glycolysis reprogramming.Journal of translational medicine · 2026Article
- Comprehensive molecular characterization identifies therapeutic vulnerabilities in ovarian clear cell carcinoma.Genome medicine · 2026Article
- Chromatin Accessibility in Cancer: Biological Functions, Mechanisms, Therapeutic Potential, and Future Directions.MedComm · 2026Review
- The research landscape and future of targeting super-enhancers for cancer therapy: a bibliometric analysis.Discover oncology · 2026Article
- Targeting super-enhancer-driven SKIL transcription by CDK7 inhibitor THZ1 to suppress gastric cancer progression.Journal of translational medicine · 2026Article
- Role of the Super-Enhancer Component Bromodomain Protein 4 in the Radiation Response of Human Head and Neck Squamous Cell Carcinoma Cells.Current issues in molecular biology · 2026Article
- The Clinical Diagnostic Value of the Super-enhancer-associated Long Noncoding RNA RP11-803D5.4 and AC005592.2 in Colorectal Cancer.Current medicinal chemistry · 2026Article
- Silencing of circRERE(4-5) inhibits ONECUT2-mediated tumorigenesis and metastasis in gastric cancer.Frontiers in immunology · 2026Article
- Tumor Electric Field Therapy Inhibits TGF-β/C1R Signaling Axis-Driven Epithelial-Mesenchymal Transition in Glioblastoma.CNS neuroscience & therapeutics · 2026Article
- Decoding macrophage heterogeneity in the pulmonary fibrosis lung cancer transition.Frontiers in immunology · 2026Review
- Long non-coding RNAs in cancer glycolysis and metabolism: mechanisms and translational opportunities.Cell death & disease · 2025Review
- LINC00592 is a predictor of poor lung adenocarcinoma outcomes that promotes tumor cell migration and invasion.Biochemistry and biophysics reports · 2025Article
- ALKBH5 demethylation modification of SE-lncRNA ZMIZ1-AS1 promotes FGFR1-mediated proliferation and invasive metastasis in osteosarcoma.Cellular and molecular life sciences : CMLS · 2025Article
- HSF2BP modulates lung adenocarcinoma proliferation and immune microenvironment via BNC1/TGF-β/SMAD3 signaling pathway.Scientific reports · 2025Article
- SMAD3 and p300 complex scaffolding by long non-coding RNA LIMD1-AS1 promotes TGF-β-induced breast cancer cell plasticity.Nucleic acids research · 2025Article
- USP14 inhibits mitophagy and promotes tumorigenesis and chemosensitivity through deubiquitinating BAG4 in microsatellite instability-high colorectal cancer.Molecular medicine (Cambridge, Mass.) · 2025Article
- STAT3 Inhibition Prevents Adaptive Resistance and Augments NK Cell Cytotoxicity to KRASCancer science · 2025Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLung adenocarcinoma (LUAD) is the leading cause of death worldwide. However, the roles of long noncoding RNAs (lncRNAs) hijacked by super-enhancers (SEs), vital regulatory elements of the epigenome, remain elusive in the progression of LUAD metastasis.
methodsSE-associated lncRNA microarrays were used to identify the dysregulated lncRNAs in LUAD. ChIP-seq, Hi-C data analysis, and luciferase reporter assays were utilized to confirm the hijacking of LINC01977 by SE. The functions and mechanisms of LINC01977 in LUAD were explored by a series of in vitro and in vivo assays.
resultsWe found that LINC01977, a cancer-testis lncRNA, was hijacked by SE, which promoted proliferation and invasion both in vitro and in vivo. LINC01977 interacted with SMAD3 to induce its nuclear transport, which facilitated the interaction between SMAD3 and CBP/P300, thereby regulating the downstream target gene ZEB1. Additionally, SMAD3 up-regulated LINC09177 transcription by simultaneously binding the promoter and SE, which was induced by the infiltration of M2-like tumor-associated macrophages (TAM2), subsequently activating the TGF-β/SMAD3 pathway. Moreover, LINC01977 expression was positively correlated with TAM2 infiltration and SMAD3 expression, especially in early-stage LUAD. Higher chromatin accessibility in the SE region of LINC01977 was observed with high expression of TGF-β. Early-stage LUAD patients with high LIN01977 expression had a shorter disease-free survival.
conclusionsTAM2 infiltration induced a rich TGF-β microenvironment, activating SMAD3 to bind the promoter and the SE of LINC01977, which up-regulated LINC01977 expression. LINC01977 also promoted malignancy via the canonical TGF-β/SMAD3 pathway. LINC01977 hijacked by SE could be a valuable therapeutic target, especially for the treatment of early-stage LUAD.
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