ArticleAnnals of translational medicine2018
H3K27me3 induces multidrug resistance in small cell lung cancer by affecting HOXA1 DNA methylation via regulation of the lncRNA HOTAIR.
Article in Annals of translational medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 61 citations in OpenAlex.
- Functional role of long non-coding RNA MALAT1 and HOTAIR in lung cancer.Non-coding RNA research · 2026Review
- Review
- Multi-omics integration in deciphering non-small cell lung cancer drug resistance: current status, challenges, and future prospects.Hereditas · 2026Review
- Diagnostic Utility and Clinicopathologic Associations of Histone H3 Lysine 27 Trimethylation (H3K27me3) Immunohistochemistry for Merkel Cell Carcinoma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2026Article
- Lung Cancer Chemoresistance: Insights into the Regulatory Role of lncRNAs.Cancer management and research · 2026Review
- Targeting FOXP1 phase separation in small cell lung cancer mechanisms of chemotherapy resistance.Communications biology · 2025Article
- Decoding LncRNA in COPD: Unveiling Prognostic and Diagnostic Power and Their Driving Role in Lung Cancer Progression.International journal of molecular sciences · 2024Review
- Overcoming Treatment Resistance in Medulloblastoma: Underlying Mechanisms and Potential Strategies.Cancers · 2024Review
- Kidney Aging and Chronic Kidney Disease.International journal of molecular sciences · 2024Review
- Role of HOXA1-4 in the development of genetic and malignant diseases.Biomarker research · 2024Review
- Novel Therapeutic Options for Small Cell Lung Cancer.Current oncology reports · 2023Review
- Review
- Long non-coding RNA MIR22HG inhibits the proliferation and migration, and promotes apoptosis by targeting microRNA-9-3p/ SOCS1 axis in small cell lung cancer cells.Molecular biology reports · 2023Article
- Interactome of Long Non-Coding RNAs: Transcriptomic Expression Patterns and Shaping Cancer Cell Phenotypes.International journal of molecular sciences · 2023Review
- The uprise of RNA biology in neuroendocrine neoplasms: altered splicing and RNA species unveil translational opportunities.Reviews in endocrine & metabolic disorders · 2023Review
- Contingent Synergistic Interactions between Non-Coding RNAs and DNA-Modifying Enzymes in Myelodysplastic Syndromes.International journal of molecular sciences · 2022Review
- Functions and underlying mechanisms of lncRNA HOTAIR in cancer chemotherapy resistance.Cell death discovery · 2022Review
- Article
- Article
- LncRNA-mediated DNA methylation: an emerging mechanism in cancer and beyond.Journal of experimental & clinical cancer research : CR · 2022Review
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) serves as a powerful predictor of tumor progression and overall survival in patients. Our previous studies showed that HOTAIR modulated HOXA1 DNA methylation by reducing DNMT1 and DNMT3b expression in drug-resistant small cell lung cancer (SCLC). Moreover, H3 lysine 27 trimethylation (H3K27me3) is catalyzed by enhancer of zeste homolog 2 (EZH2) and plays a critical role in SCLC chemoresistance. However, it is not completely clear whether H3K27me3 affects HOXA1 DNA methylation or whether this effect is mediated by HOTAIR.
methodsThe levels of EZH2 and H3K27me3 were identified in SCLC tissues by immunohistochemical (IHC) staining and in SCLC multidrug-resistant cells by Western blotting. Cell counting kit-8 (CCK-8) and flow cytometry were used to detect and analyze the biological function of H3K27me3. Then, we assessed the role of HOTAIR in the regulation of EZH2 and H3K27me3 by using lentivirus and small interfering RNA. Further, bisulfite sequencing PCR was conducted to detect the methylation levels of HOXA1 DNA. Finally, Western blotting was performed to examine the regulatory role of H3K27me3 in controlling HOTAIR expression in SCLC.
resultsIn this study, we found that EZH2 and H3K27me3 levels were markedly higher in SCLC tissues and multidrug-resistant SCLC cells. The results indicated that H3K27me3 was related to multidrug resistance. HOTAIR overexpression and knockdown showed that EZH2 and H3K27me3 were regulated by HOTAIR. Moreover, H3K27me3 affected HOXA1 DNA methylation levels. Strikingly, we found that H3K27me3 acted as a negative feedback regulator of HOTAIR.
conclusionsOur study showed that H3K27me3 affects HOXA1 DNA methylation via HOTAIR regulation, indicating that H3K27me3 may be a potential therapy target for SCLC chemoresistance.
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