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: Journal of Translational Medicine

Article Title: m6A methylation-modified ETV1 drives multiple myeloma progression and M2 polarization of tumor-associated macrophage through transcriptional activation of RBMS1

doi: 10.1186/s12967-026-07799-7

Figure Lengend Snippet: ETV1 promotes MM cell proliferation and cell cycle progression. ( A ) Cell viability was measured by CCK-8 assay. ( B ) Cell proliferation was determined by colony formation assay. ( C ) Cell cycle distribution was detected by flow cytometry. ( D ) The expression of cyclinD1 in MM cells was tested by western blot. Data are mean ± SD. ##, p < 0.01; ###, p < 0.001; ####, p < 0.0001

Article Snippet: The membranes were then incubated overnight at 4 °C with the following primary antibodies: human ETV1 (1: 1000 dilution, AP51197, Abcepta), human cyclinD1 (1: 5000 dilution, 26939-1-AP, Proteintech, Wuhan, China), human RBMS1 (1: 1000 dilution, 11061-2-AP, Proteintech) and human CCL2 (1: 500 dilution, 507277, Zen-bioscience, Chengdu, China).

Techniques: CCK-8 Assay, Colony Assay, Flow Cytometry, Expressing, Western Blot

Journal: Journal of Translational Medicine

Article Title: m6A methylation-modified ETV1 drives multiple myeloma progression and M2 polarization of tumor-associated macrophage through transcriptional activation of RBMS1

doi: 10.1186/s12967-026-07799-7

Figure Lengend Snippet: RBMS1 knockdown counteracts the effect of ETV1 overexpression on MM cell proliferation and M2 polarization of TAMs. ( A ) siRNAs targeting RBMS1 were transfected into RPMI8226 cells. After 48 h, the knockdown efficiency of RBMS1 in cells was verified by qPCR. ( B ) Cell viability was measured by CCK-8 assay. ( C ) Cell cycle distribution was detected by flow cytometry. ( D ) The expression of cyclinD1 in cells was detected by western blot. ( E ) The levels of CCL2 in the cell supernatant were determined by ELISA. ( F ) M2 polarization of TAMs was tested by Transwell co-culture system. M0 macrophages were seeded into the lower chamber, and MM cells were seeded into the upper chamber. After 48 h of co-culture, the expression of CD163 and CD206 in M0 macrophages were determined by qPCR. ( G ) The proportion of CD206 + cells and MFI in M0 macrophages were examined by flow cytometry. Data are mean ± SD. #, p < 0.05; ##, p < 0.01; ###, p < 0.001; ####, p < 0.0001

Article Snippet: The membranes were then incubated overnight at 4 °C with the following primary antibodies: human ETV1 (1: 1000 dilution, AP51197, Abcepta), human cyclinD1 (1: 5000 dilution, 26939-1-AP, Proteintech, Wuhan, China), human RBMS1 (1: 1000 dilution, 11061-2-AP, Proteintech) and human CCL2 (1: 500 dilution, 507277, Zen-bioscience, Chengdu, China).

Techniques: Knockdown, Over Expression, Transfection, CCK-8 Assay, Flow Cytometry, Expressing, Western Blot, Enzyme-linked Immunosorbent Assay, Co-Culture Assay

Journal: iScience

Article Title: Prognostic value of BTG1 for predicting decitabine sensitivity in de novo acute myeloid leukemia

doi: 10.1016/j.isci.2025.114327

Figure Lengend Snippet: Downstream signaling pathway of BTG1 in AML cell lines (A) Top three signaling pathways in terms of Gene Ratio were EBV infection (0.037), Wnt signaling pathway (0.035), and hematopoietic lineage (0.023) of KEGG pathway enrichment. (B) Effect of BTG1 on the mRNA expression of β-catenin, Cyclin D1, and C-Myc. (C) Effect of BTG1 on the protein expression of β-catenin and Cyclin D1. (D) The relative viability of AML cells after interference of BTG1 and treatment with FH535. (E) Apoptosis of AML cells after interference of BTG1 and treatment with FH535. Data are presented as mean ± standard deviation (SD). (ns, p > 0.05; ∗ p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001; ∗∗∗∗ p < 0.0001).

Article Snippet: Mouse monoclonal anti-human Cyclin D1 , Proteintech , Cat# 60186-1-Ig RRID: AB_10793718.

Techniques: Protein-Protein interactions, Infection, Expressing, Standard Deviation

Journal: PLOS One

Article Title: STAG2 mutations in the normal colon induce upregulation of oncogenic pathways in neighbouring wildtype cells

doi: 10.1371/journal.pone.0332499

Figure Lengend Snippet: a. Heatmap depicting the top 20 differentially expressed genes between STAG2 wildtype and mutant populations. b. Using gene set enrichment analysis (GSEA), only the “HALLMARK_TNFA_SIGNALING_VIA_NFKB” gene set was upregulated in wildtype compared to mutant (Normalised enrichment score: 1.75, False discovery rate q -value: 0.078). c. On immunofluorescence staining, we observed increased proliferation of wildtype organoids relative to STAG2 mutants when stained with anti-KI67 antibody. d. Fluorescent intensity of anti-KI67 antibody was statistically significantly upregulated in co-cultured wildtype organoids relative to STAG2 mutant organoids. e. We also observed increased tumorigenicity of wildtype organoids relative to STAG2 mutants when stained with anti-CCND1 antibody. f. Fluorescent intensity of anti-KI67 antibody was statistically significantly upregulated in co-cultured wildtype organoids relative to STAG2 mutant organoids. Scale bars are 50µm. All experiments were performed with N = 3 biological replicates.

Article Snippet: Primary antibodies used included rabbit anti-human STAG2 antibody (1:100, 19837–1-AP, Proteintech, USA), mouse anti-human KI67 antibody (1:500, 66555–6-Ig, Proteintech, USA), mouse anti-human P53 antibody (1:400, 60283–2-Ig, Proteintech, USA), mouse anti-human CCND1 antibody (1:100, 60186–1-Ig, Proteintech, USA), mouse anti-human TERT antibody (1: 100, MA5−16033, Invitrogen, USA), mouse anti-human KRAS antibody (1:250, 415700, Invitrogen, USA), and mouse anti-human TNFα antibody (1:50, MA5−23720, Invitrogen, USA).

Techniques: Mutagenesis, Immunofluorescence, Staining, Cell Culture

Journal: International Journal of Molecular Sciences

Article Title: White Adipocyte Stem Cell Expansion Through Infant Formula Feeding: New Insights into Epigenetic Programming Explaining the Early Protein Hypothesis of Obesity

doi: 10.3390/ijms26104493

Figure Lengend Snippet: Predicted differences in microRNA (miR)-mediated adipogenic gene regulation between formula feeding and breastfeeding. ( A ) Formula feeding with increased protein intake and deficient miR supply increases the expression of FTO . FTO-mediated m 6 A demethylation enhances gene expression of activators of cell cycle progression ( MYC , CCND1 ), adipogenic transcription factors ( PPARG , CEBPA , CEBPB ), ATF4 (increasing leucine (Leu)-mediated mTORC1/S6K1 activation), upregulation of FLOT2 (promoting adipogenic extracellular matrix (ECM) changes), upregulation of PDGFRB (increasing adipocyte precursor cell (APC) retention in the vascular niche as well as enhanced VEGFA expression (increasing angiogenesis and APC niche expansion) synergistically promoting adipocyte stem cell (ASC) mitotic clonal expansion (MCE), wingless (WNT) suppression-regulated ASC commitment and adipogenesis. ( B ) Early lactation-derived breast milk exosomal miRs attenuate FTO expression resulting in reduced expression of FTO-activated adipogenic transcription factors and regulators of ASC development (green color) in the vascular niche and ECM. Increased Wnt signaling attenuates ASC commitment and APC expansion adjusting ASC numbers and differentiation. Complete names of gene symbols are provided in the list of abbreviations. FTO-regulated genes are presented in green color.

Article Snippet: MiR-34a-5p , CCND1 CCNE1 CDK2 CDK4 CDK6 PDGFRB CTRP9 FLOT2 , Cyclin D1 ↓ , inhibition of ASC differentiation, MCE ↓ Cyclin D1 ↓ Cyclin-dependent kinase 2 ↓ Cyclin-dependent kinase 4 ↓ Cyclin-dependent kinase 6 Platelet-derived growth factor receptor B ↓ , suppression of ASC niche formation Suppression of ASC proliferation and migration Flotillin 2 ↓ , suppression of pro-adipogenic ECM , [ ] [ , ] [ ] [ , ] .

Techniques: Expressing, Gene Expression, Activation Assay, Derivative Assay