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pmid:40287899
MPC2 Overexpression Drives Mitochondrial Oxidative Phosphorylation and Promotes Progression in Diffuse Large B-Cell Lymphoma.
Haoneng Wu · Qiuran Zhao · Xiaobo Ma · Ying Zhao · Qing Wang · Jinguang Bai · Songling Huang
Biochemical genetics · 2025 doi:10.1007/s10528-025-11100-8
Paper
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Experiment
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Data
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Analysis
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Complete file
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Altered metabolism, particularly mitochondrial function, has emerged as a critical factor in cancer progression. However, the role of mitochondrial metabolism in DLBCL remains poorly understood. This study aimed to identify key mitochondrial factors associated with DLBCL progression. We analyzed transcriptomic data from multiple DLBCL datasets (GSE83632, TCGA-GTEX, GSE181063, GSE4475) using differential expression analysis, weighted gene co-expression network analysis (WGCNA), and Gene Set Enrichment Analysis (GSEA). The expression and function of the identified key factor, Mitochondrial Pyruvate Carrier 2 (MPC2), were validated using clinical samples, DLBCL cell lines, and an in vivo mouse model of xenograft. Integrative bioinformatics analysis identified MPC2 as a significantly upregulated gene in DLBCL, associated with enrichment of oxidative phosphorylation (OXPHOS) and cell cycle-related genes. MPC2 overexpression was confirmed in clinical DLBCL samples and cell lines at both mRNA and protein levels. Knockdown of MPC2 in DLBCL cells impaired mitochondrial OXPHOS, increased glycolysis, and suppressed cell proliferation, invasion, and 3D spheroid formation. In vivo, MPC2 silencing significantly reduced tumor growth in a xenograft mouse model. Our findings reveal MPC2 as a key regulator of mitochondrial function in DLBCL, promoting tumor progression through enhanced OXPHOS. This study provides new insights into the metabolic reprogramming of DLBCL and suggests MPC2 as a potential therapeutic target for this aggressive lymphoma.", "claims": [{"id": "claim-method", "statement": "Differential gene expression analysis was performed using the limma package (v3.46.0) in R (v4.1.0). Weighted gene co-expression network analysis (WGCNA) was conducted using the WGCNA package (v1.70-3) in R. 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We analyzed transcriptomic data from multiple DLBCL datasets (GSE83632,"], "order_basis": "paper_text_order:508", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["al samples, DLBCL cell lines, and an in vivo mouse model of xenograft. Integrative bioinformatics ana", "ficantly reduced tumor growth in a xenograft mouse model. Our findings reveal MPC2 as a key regulator", "g clinical samples, DLBCL cell lines, and an in vivo mouse model of xenograft. Integrative bioinf", "ration, invasion, and 3D spheroid formation. In vivo, MPC2 silencing significantly reduced tumor"], "order_basis": "paper_text_order:897", "id": "assay:2"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["cell lines at both mRNA and protein levels. Knockdown of MPC2 in DLBCL cells impaired mitochondria"], "order_basis": "paper_text_order:1233", "id": "assay:3"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["ere used for all experiments. All cells were cultured in RPMI-1640 medium (Gibco, Thermo Fisher Scien"], "order_basis": "paper_text_order:3083", "id": "assay:4"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["th GSE83632 and GTEX–TCGA dataset (Fig. 3A). Immunohistochemical staining data from Human Protein Atlas (HPA)", "amples in GSE83632 and GTEX–TCGA datasets. B Immunohistochemical staining images of MPC2 in normal and DLBCL"], "order_basis": "paper_text_order:4026", "id": "assay:5"}, {"role": "data_generation", "definition_id": "clinical_cohort", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["DLBCL patients (Fig. 3B). Furthermore, DLBCL patients with high levels of MPC2 expression showed a redu", "l (Fig. 3C). We further collected peripheral blood samples from normal controls and DLBCL patients. Both qRT", "sults showing MPC2 mRNA levels in peripheral blood samples from normal controls and DLBCL patients (n = 10 s", "nalysis of MPC2 protein levels in peripheral blood samples from normal controls and DLBCL patients. F qRT-PC"], "order_basis": "paper_text_order:4219", "id": "assay:6"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["nd DLBCL patients. Both qRT-PCR analysis and western blot results confirmed the upregulation of MPC2 i", "atients (n = 10 samples in each category). E Western blot analysis of MPC2 protein levels in periphera", "LBCL cell lines (SU-DHL-4, U-2932, HBL-1). G Western blot analysis comparing MPC2 protein levels betwe"], "order_basis": "paper_text_order:4422", "id": "assay:7"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Differential gene expression analysis was performed using the limma package (v3.46.0) in R (v4.1.0). Weighted gene co-expression network analysis (WGCNA) was conducted using the WGCNA package (v1.70-3) in R. Gene Set Enrichment Analysis (GSEA) was performed using the clusterProfiler package (v4.0.5) in R."], "order_basis": "consumes_earlier_output", "id": "assay:8"}]}