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pmid:38692009
The mechanism of mitochondrial metabolic gene PMAIP1 involved in Alzheimer's disease process based on bioinformatics analysis and experimental validation.
Yingchun Ling · Lingmin Hu · Jie Chen · Mingyong Zhao · Xinyang Dai
Clinics (Sao Paulo, Brazil) · 2024 doi:10.1016/j.clinsp.2024.100373
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Experiment
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Complete file
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Differentially Expressed Genes (DEGs) were screened using the \"limma\" R package, and the biological functions and pathways were investigated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The LASSO algorithm was used to identify the candidate center genes and validated in the GSE97760 dataset. PMAIP1 with the highest diagnostic value was selected and its effect on the occurrence of AD by biological experiments.\nRESULTS: A sum of 364 DEGs and 50 hub genes were ascertained. GO and KEGG enrichment analysis demonstrated that DEGs were preponderantly associated with cell metabolism and apoptosis. Five genes most associated with AD as candidate central genes by LASSO algorithm analysis. Then, the expression level and specificity of candidate central genes were verified by GSE97760 dataset, which confirmed that PMAIP1 had a high diagnostic value. Finally, the regulatory effects of PMAIP1 on apoptosis and mitochondrial function were detected by siRNA, flow cytometry and Western blot. siRNA-PMAIP1 can alleviate mitochondrial dysfunction and inhibit cell apoptosis.\nCONCLUSION: This study identified biomarkers related to mitochondrial metabolism in AD and provided a theoretical basis for the diagnosis of AD. 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Five genes most associated with AD as candi", "Finally, the regulatory effects of PMAIP1 on apoptosis and mitochondrial function were detected by", "e mitochondrial dysfunction and inhibit cell apoptosis. CONCLUSION: This study identified biomarker", "sis showed that these genes were enriched in Apoptosis and Hippo signaling regulation pathways (Fig"], "order_basis": "paper_text_order:1089", "id": "assay:1"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["and mitochondrial function were detected by siRNA, flow cytometry and Western blot. siRNA-PMAI", "d by siRNA, flow cytometry and Western blot. siRNA-PMAIP1 can alleviate mitochondrial dysfuncti"], "order_basis": "paper_text_order:1453", "id": "assay:2"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["tochondrial function were detected by siRNA, flow cytometry and Western blot. siRNA-PMAIP1 can alleviate"], "order_basis": "paper_text_order:1459", "id": "assay:3"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["n were detected by siRNA, flow cytometry and Western blot. siRNA-PMAIP1 can alleviate mitochondrial dy"], "order_basis": "paper_text_order:1478", "id": "assay:4"}, {"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["Materials and methods Microarray data processing Three microarray datasets (G", "and methods Microarray data processing Three microarray datasets (GSE5281, GSE28146, and GSE97760) o", "ent-039494 SurePrint G3 Human GE v2 8 × 60 K Microarray 039381). In addition, this study is a diagno", "l samples. They are all based on the GPL570 (Affymetrix Human Genome U133 Plus 2.0 Array) platform."], "order_basis": "paper_text_order:1913", "id": "assay:5"}, {"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": ["iences (Shanghai, China), and the cells were cultured in Dulbecco's Modified Eagle's Medium (DMEM) wi"], "order_basis": "paper_text_order:2891", "id": "assay:6"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The “limma” package in R software (Version 4.3.1) was utilized to screen DEGs between the AD patients and control samples."], "order_basis": "consumes_earlier_output", "id": "assay:7"}]}