ArticleClinical epigenetics2019
Targeted design and identification of AC1NOD4Q to block activity of HOTAIR by abrogating the scaffold interaction with EZH2.
Article in Clinical epigenetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 84 citations in OpenAlex.
- Interrelation between lncRNA HOTAIR and EZH2 expression and progression free survival during endocrine treatment in breast cancer.BMC cancer · 2026Article
- Long non-coding RNAs in B-cell acute lymphoblastic leukemia: Disease implication, challenges and therapeutic opportunities.Non-coding RNA research · 2026Review
- Noncoding RNA in Clinical Trials: Diagnostic and Therapeutical Prospects.Experientia supplementum (2012) · 2026Review
- Vitamin D as an Epigenetic Regulator: A Hypothetical Mechanism for Cancer Prevention via Inhibition of Oncogenic lncRNA HOTAIR.International journal of molecular sciences · 2025Article
- Rethinking RNA Modifications: Therapeutic Strategies for Targeting Dysregulated RNA.Journal of molecular biology · 2025Review
- Molecular Mechanisms and Therapeutic Implications of Long Non-coding RNAs in Cutaneous Biology and Disease.Journal of cellular physiology · 2025Review
- HOTAIR in cancer: diagnostic, prognostic, and therapeutic perspectives.Cancer cell international · 2024Review
- Article
- The multifaceted functions of long non-coding RNAExpert reviews in molecular medicine · 2024Review
- Roles of HOTAIR Long Non-coding RNA in Gliomas and Other CNS Disorders.Cellular and molecular neurobiology · 2024Review
- CRISPR-Cas9 library screening combined with an exosome-targeted delivery system addresses tumorigenesis/TMZ resistance in the mesenchymal subtype of glioblastoma.Theranostics · 2024Article
- The role of HOTAIR in the modulation of resistance to anticancer therapy.Frontiers in molecular biosciences · 2024Review
- Hidden regulators: the emerging roles of lncRNAs in brain development and disease.Frontiers in neuroscience · 2024Review
- The role of long non-coding RNAs and circular RNAs in cervical cancer: modulating miRNA function.Frontiers in cell and developmental biology · 2024Review
- Regulatory RNAs: role as scaffolds assembling protein complexes and their epigenetic deregulation.Exploration of targeted anti-tumor therapy · 2024Review
- Strategic and Innovative Roles of lncRNAs Regulated by Naturally-derived Small Molecules in Cancer Therapy.Current medicinal chemistry · 2024Review
- EPIC-0307-mediated selective disruption of PRADX-EZH2 interaction and enhancement of temozolomide sensitivity to glioblastoma via inhibiting DNA repair and MGMT.Neuro-oncology · 2023Article
- The lncRNA HOTAIR: a pleiotropic regulator of epithelial cell plasticity.Journal of experimental & clinical cancer research : CR · 2023Review
- Long Non-Coding RNAs as Emerging Targets in Lung Cancer.Cancers · 2023Review
- A novel compound EPIC-0412 reverses temozolomide resistance via inhibiting DNA repair/MGMT in glioblastoma.Neuro-oncology · 2023Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNearly 25% of long intergenic non-coding RNAs (lincRNAs) recruit chromatin-modifying proteins (e.g., EZH2) to silence target genes. HOX antisense intergenic RNA (HOTAIR) is deregulated in diverse cancers and could be an independent and powerful predictor of eventual metastasis and death. Yet, it is challenging to develop small molecule drugs to block activity of HOTAIR with high specificity in a short time.
resultsOur previous study proved that the 5' domain, but not its 3' domain, was the function domain of HOTAIR responsible for tumorigenesis and metastasis in glioblastoma and breast cancer, by recruiting and binding EZH2. Here, we targeted to establish a structure-based methodology to identify lead compounds of HOTAIR, by abrogating scaffold interactions with EZH2. And a small compound AC1NOD4Q (ADQ) was identified by high-throughput molecular docking-based virtual screening of the PubChem library. Our analysis revealed that ADQ was sufficiently and specifically interfering HOTAIR/EZH2 interaction, thereby impairing the H3K27-mediated tri-methylation of NLK, the target of HOTAIR gene, and consequently inhibiting tumor metastasis through Wnt/β-catenin pathway in vitro and in orthotopic breast cancer models. The results of RIP and EMSA further revealed that 36G46A of 5' domain was the essential binding site for ADQ exerted its inhibitory effect, further narrowed the structure and function of HOTAIR from the 5' functional domain to the micro-domain.
conclusionsOur findings suggest of a potential new strategy to discover the lead compound for targeted lincRNA therapy and potentially pave the way for exploiting ADQ as a scaffold for more effective small molecule drugs.
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