Browsing by Subject "KMT2D"

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    Mechanism of KMT2D-mediated epigenetic modification in IL-1β-induced nucleus pulposus cell degeneration
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Liu, Hongjiang; Liu, Haiquan; Meng, Zuyu; Zhang, Wensheng
    Background. Intervertebral disc (IVD) degeneration (IVDD) is characterized by structural destruction accompanied by accelerated signs of aging. This study aimed to investigate the mechanism of lysine methyltransferase 2D (KMT2D) in the proliferation, apoptosis, and inflammation of nucleus pulposus cells (NPCs) in IVDD. Methods. Mouse-derived NPCs were cultured and induced with interleukin-1 beta (IL-1β) to establish cell models. KMT2D expression was detected by western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). KMT2D expression was interfered with, and the contents of IL-18, IL-6, and tumor necrosis factor (TNF) were detected by enzyme-linked immunosorbent assay. Cell proliferation, apoptosis, and the expression of miR-133a-5p and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2) were measured. The enrichment of KMT2D and Histone 3 Lysine 4 monomethylation/dimethylation (H3K4me1/2) on the miR-133a-5p promoter was analyzed by chromatin immunoprecipitation and qPCR. The binding of miR-133a-5p and PFKFB2 was analyzed by a dual-luciferase assay. Results. IL-1β treatment promoted KMT2D expression in NPCs. KMT2D knockdown reduced inflammation and apoptosis and promoted the proliferation of IL-1β-induced NPCs. Mechanistically, KMT2D upregulated miR-133a-5p expression by increasing the level of H3K4me2 at the miR-133a-5p promoter, thereby promoting the binding between miR-133a-5p and PFKFB2 and downregulating the transcription of PFKFB2. miR-133a-5p overexpression or PFKFB2 knockdown alleviated the protective effect of KMT2D knockdown on IL-1β-induced NPCs. Conclusion. KMT2D promoted miR-133a-5p expression through H3K4me2 methylation, thereby promoting the binding of miR-133a-5p to PFKFB2, reducing the mRNA level of PFKFB2, promoting inflammation and apoptosis of IL-1β-induced NPCs, and inhibiting NPC proliferation.
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    The role of KMT2 gene in human tumors
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Zhang, Zhi Long; Yu, Peng Fei; Ling, Zhi Qiang
    Histone methylation plays a crucial role in the regulation of gene transcriptional expression, and aberration of methylation-modifying enzyme genes can lead to a variety of genetic diseases, including human cancers. The histone modified protein KMT2 (lysin methyltransferase) family are involved in cell proliferation, growth, development and differentiation through regulating gene expression, and are closely related with many blood cancers and solid tumors. In recent years, several studies have shown that mutations in the KMT2 gene occur frequently in a variety of human cancers and the mutation status of the KMT2 gene may be correlated with the occurrence, development and prognosis of some tumors. Research uncovering the clinical characteristics and molecular mechanisms of KMT2 mutation in human tumors will be helpful for early diagnosis and prognosis of tumors as well as drug development for targeted therapies.