Histone 3 lysine-27 demethylase KDM6A coordinates with KMT2B to play an oncogenic role in NSCLC by regulating H3K4me3
| Autor: | Xuejiao Leng, Yile Sun, Na An, Xue Wang, Jianfeng Wang, Zhiwei Chen |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Cancer Research Lung Neoplasms Carcinogenesis Kaplan-Meier Estimate medicine.disease_cause Epigenesis Genetic Histones Mice 0302 clinical medicine Carcinoma Non-Small-Cell Lung RNA-Seq Lung Wnt Signaling Pathway Regulation of gene expression Aged 80 and over Histone Demethylases Gene knockdown biology Wnt signaling pathway Middle Aged Prognosis Gene Expression Regulation Neoplastic Survival Rate Histone 030220 oncology & carcinogenesis Gene Knockdown Techniques Female Adult 03 medical and health sciences Genetics medicine Animals Humans Epigenetics Molecular Biology Aged Retrospective Studies Histone-Lysine N-Methyltransferase Xenograft Model Antitumor Assays respiratory tract diseases 030104 developmental biology A549 Cells Cancer research biology.protein H3K4me3 Demethylase Follow-Up Studies |
| Zdroj: | Oncogene. 39(41) |
| ISSN: | 1476-5594 |
| Popis: | Aberrations in epigenetic modulation dysregulate transcription, playing a critical role in the developmental process of tumors, including lung cancer. Aberrant levels of the histone 3 lysine-27 demethylase KDM6A have been found in cancer and are either positively or negatively associated with tumorigenesis and prognosis. However, the clinical relevance and functional role of KDM6A in lung cancer is largely unknown. We found that KDM6A protein expression was higher in NSCLC tissues than in the corresponding paracancer tissues and that high KDM6A expression was associated with poor patient prognosis. Furthermore, KDM6A knockdown in NSCLC cell lines markedly inhibited the tumorigenic phenotype both in vitro and in vivo. Mechanistically, KDM6A colocalized and cooperated with KMT2B to reprogram the transcriptional network via regulating the cancer pathway, in which abnormal activation of the Wnt pathway is the dominant factor. Interestingly, in NSCLC cell lines, H3K4me3 but not H3K27me2/3 or H3K4me1/2 was markedly altered upon KDM6A or KMT2B knockdown, indicating that KDM6A may act independently of H3K27 demethylases in NSCLC. Taken together, these results indicated that KDM6A or KMT2B may be a prognostic biomarker and promising therapeutic target in NSCLC. |
| Databáze: | OpenAIRE |
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