Journal: International Journal of Molecular Medicine

Article Title: m 6 A in adipose tissue inflammation: A novel regulator of obesity and metabolic diseases (Review)

doi: 10.3892/ijmm.2026.5795

Figure Lengend Snippet: Role of m 6 A in adipogenesis. Insufficient adipogenesis in adipose tissue leads to persistent, chronic inflammation. m 6 A modification plays a crucial role in all stages of adipogenesis, from commitment to terminal differentiation. During commitment, METTL3 promotes lipogenic differentiation in BMSCs by regulating the m 6 A levels of PTH1R and JAK1, whereas silencing METTL14 reduces the expression of SMAD1, inhibiting BMSC proliferation. During terminal differentiation, m 6 A regulates MCE and the transition to mature adipocytes. FTO influences key genes such as ATG5, ATG7 and JAK2, affecting autophagy, STAT3 phosphorylation and adipogenesis. FTO knockout increases the m 6 A levels of CCND1 and CDK2, blocking MCE. m 6 A, N6-methyladenine; METTL, methyltransferase-like; PTH1R, parathyroid hormone 1 receptor; JAK, Janus kinase; BMSC, bone marrow mesenchymal stem cell; MCE, mitotic clone amplification; FTO, Fat mass and obesity-associated protein; ATG, autophagy-related; STAT3, signal transducer and activator of transcription 3; CCND1, cyclin D1; CDK2, cyclin-dependent kinase 2; IGF2BP1, insulin-like growth factor 2 mRNA-binding protein 1; YTHDF2, YTH domain family 2.

Article Snippet: In addition, for mitotic clone amplification (MCE) in the early stage of terminal differentiation, the inhibition of FTO expression in 3T3-L1 cells leads to increased m 6 A methylation levels of cyclin D1 (CCND1) and cyclin-dependent kinase 2, the protein expression of which is reduced after recognition by YTHDF2, resulting in blockade of the MCE process and in turn the inhibition of lipogenesis ( ) ( ).

Techniques: Modification, Expressing, Phospho-proteomics, Knock-Out, Blocking Assay, Amplification, Binding Assay

Journal: International Journal of Molecular Medicine

Article Title: m 6 A in adipose tissue inflammation: A novel regulator of obesity and metabolic diseases (Review)

doi: 10.3892/ijmm.2026.5795

Figure Lengend Snippet: Role of m 6 A in ATMs. ATMs are deeply involved in adipose tissue inflammation, and m 6 A plays critical roles in macrophage biology, including their development, activation, pyroptosis and metabolism of lipids. (A) m 6 A regulates macrophage development by targeting genes such as CCND1 and ATRX via YTHDF3, ALKBH5 and METTL3, affecting haematopoietic stem and progenitor cell differentiation. (B) m 6 A modification mediated by METTL3, METTL14 and IGF2BP2 controls macrophage activation and polarization by influencing key genes such as SPRED2, MYD88 and STAT1, which impact the NF-κB and PPAR-γ pathways. (C) m 6 A regulates macrophage pyroptosis by targeting CASPASE-1, IL-1β and MALAT1 and modulating pathways such as the PTBP1/USP8/TAK1 pathway. (D) Additionally, m 6 A affects macrophage lipid metabolism by regulating lipid uptake and cholesterol efflux through MSR1 and SR-B1. m 6 A, N6-methyladenine; ATMs, adipose tissue macrophages; CCND1, cyclin D1; ATRX, α-thalassemia X-linked intellectual disability syndrome; YTHDF3, YTH domain family 3; ALKBH5, alkB homologue 5; METTL, methyltransferase-like; IGF2BP2, insulin-like growth factor 2 mRNA-binding protein 2; SPRED2, sprouty-related EVH1 domain-2; MYD88, myeloid differentiation primary response 88; STAT1, signal transducer and activator of transcription 1; NF-κB, nuclear factor-κB; PPAR-γ, peroxisome proliferator-activated receptor γ; CASPASE-1, cysteinyl aspartate specific proteinase-1; IL, interleukin; MALAT1, metastasis-associated lung adenocarcinoma transcript 1; PTBP1, polypyrimidine tract-binding protein 1; USP8, ubiquitin-specific peptidase 8; TAK1, TGFβ-activated kinase 1; MSR1, macrophage scavenger receptor 1; SR-B1, scavenger receptor type B1; ROS, reactive oxygen species; TSC1, tuberous sclerosis complex 1; SOCS2, suppressor of cytokine signalling 2; GSDMD-N, gasdermin D N-terminal domain; OxLDL, oxidized low-density lipoprotein; MSR1, macrophage scavenger receptor 1; DDX5, DEAD-box helicase 5; MEHP, mono(2-ethylhexyl) phthalate.

Article Snippet: In addition, for mitotic clone amplification (MCE) in the early stage of terminal differentiation, the inhibition of FTO expression in 3T3-L1 cells leads to increased m 6 A methylation levels of cyclin D1 (CCND1) and cyclin-dependent kinase 2, the protein expression of which is reduced after recognition by YTHDF2, resulting in blockade of the MCE process and in turn the inhibition of lipogenesis ( ) ( ).

Techniques: Activation Assay, Cell Differentiation, Modification, Binding Assay, Ubiquitin Proteomics

Journal: Anti-Cancer Drugs

Article Title: Hematopoietic progenitor kinase 1 inhibitor BGB-15025 induces apoptosis in acute myeloid leukemia cells through the cell cycle pathway and mitogen-activated protein kinase/extracellular signal-regulated kinase pathway signaling axis

doi: 10.1097/CAD.0000000000001794

Figure Lengend Snippet: BGB-15025 inhibits the cell cycle and the MAPK/ERK signaling pathway in AML cells. (a) KEGG analysis revealed that differentially expressed genes were significantly enriched in relevant signaling pathways. (b) GSEA of differentially expressed genes in the treated group, compared with the control group, indicated a predominant enrichment in cell cycle-related pathways. (c) Two AML cell lines (KG1A and THP-1) were exposed to different concentrations of BGB-15025, and the expression levels of CCND1 , CDK4 , and P21 genes were quantified using qRT-PCR. (d) Various concentrations of BGB-15025 were administered to two AML cell lines (KG1A and THP-1), followed by the detection of cyclin D1, CDK4, and P21 protein expressions via Western blot analysis. (f) Different concentrations of BGB-15025 were administered to two AML cell lines, KG1A and THP-1. The expression levels of ERK, p-ERK, P38, and p-P38 proteins were assessed using Western blot analysis. Data presented are derived from at least three independent experiments. Statistical significance was determined as follows: * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001 when compared with the control group. (e and g) The effect of HPK1 knockdown on the expression of the above-mentioned proteins was assessed in AML (THP-1) cells. AML, acute myeloid leukemia; GSEA, Gene Set Enrichment Analysis; HPK1, hematopoietic progenitor kinase 1; KEGG, Kyoto Encyclopedia of Genes and Genomes; MAPK/ERK, mitogen-activated protein kinase/extracellular signal-regulated kinase; qRT-PCR, quantitative real-time PCR.

Article Snippet: Membranes were subsequently incubated overnight at 4 °C with specific primary antibodies: β-actin (#4970; 1 : 1000), HPK1 (#46510; 1 : 1000), cyclin D1 (#55506; 1 : 1000), P21 (#2947; 1 : 1000), ERK (#4696; 1 : 1000), phosphorylated ERK (p-ERK, #4370; 1 : 1000), P38 MAPK (#8690; 1 : 1000), and phosphorylated P38 MAPK (p-P38, #9211; 1 : 1000) (all from Cell Signaling Technology, Danvers, Massachusetts, USA).

Techniques: Protein-Protein interactions, Control, Expressing, Quantitative RT-PCR, Western Blot, Derivative Assay, Knockdown, Real-time Polymerase Chain Reaction