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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

Paper

complete

Experiment

complete

Data

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Analysis

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Execution

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pmid:38692009
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title
The mechanism of mitochondrial metabolic gene PMAIP1 involved in Alzheimer's disease process based on bioinformatics analysis and experimental validation.
doi
10.1016/j.clinsp.2024.100373
pmid
38692009
authors array · 5 items
[0]
Yingchun Ling
[1]
Lingmin Hu
[2]
Jie Chen
[3]
Mingyong Zhao
[4]
Xinyang Dai
journal
Clinics (Sao Paulo, Brazil)
year
2024
abstract
OBJECTIVES: This study explored novel biomarkers that can affect the diagnosis and treatment in Alzheimer's Disease (AD) related to mitochondrial metabolism. METHODS: The authors obtained the brain tissue datasets for AD from the Gene Expression Omnibus (GEO) and downloaded the mitochondrial metabolism-related genes set from MitoCarta 3.0 for analysis. 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. RESULTS: 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. CONCLUSION: This study identified biomarkers related to mitochondrial metabolism in AD and provided a theoretical basis for the diagnosis of AD. PMAIP1 was a potential candidate gene that may affect mitochondrial function in Hippocampal neuronal cells, and its mechanism deserves further study.
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The “limma” package in R software (Version 4.3.1) was utilized to screen DEGs between the AD patients and control samples.
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Data availability statementThe GEO datasets used in this study are available in the GEO database (https://www.ncbi.nlm.nih.gov/geo/) with the following data accession identifiers: GSE5281, GSE28146, and GSE97760.
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Data availability statementThe GEO datasets used in this study are available in the GEO database (https://www.ncbi.nlm.nih.gov/geo/) with the following data accession identifiers: GSE5281, GSE28146, and GSE97760.
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A sum of 364 DEGs and 50 hub genes were ascertained.
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A sum of 364 DEGs and 50 hub genes were ascertained.
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Microarray analyses of laser-captured hippocampus reveal distinct gray and white matter signatures associated with incipient Alzheimer’s disease
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derantly associated with cell metabolism and apoptosis. Five genes most associated with AD as candi
[1]
Finally, the regulatory effects of PMAIP1 on apoptosis and mitochondrial function were detected by
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e mitochondrial dysfunction and inhibit cell apoptosis. CONCLUSION: This study identified biomarker
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sis showed that these genes were enriched in Apoptosis and Hippo signaling regulation pathways (Fig
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and mitochondrial function were detected by siRNA, flow cytometry and Western blot. siRNA-PMAI
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tochondrial function were detected by siRNA, flow cytometry and Western blot. siRNA-PMAIP1 can alleviate
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n were detected by siRNA, flow cytometry and Western blot. siRNA-PMAIP1 can alleviate mitochondrial dy
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Materials and methods Microarray data processing Three microarray datasets (G
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and methods Microarray data processing Three microarray datasets (GSE5281, GSE28146, and GSE97760) o
[2]
ent-039494 SurePrint G3 Human GE v2 8 × 60 K Microarray 039381). In addition, this study is a diagno
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l samples. They are all based on the GPL570 (Affymetrix Human Genome U133 Plus 2.0 Array) platform.
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iences (Shanghai, China), and the cells were cultured in Dulbecco's Modified Eagle's Medium (DMEM) wi
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The “limma” package in R software (Version 4.3.1) was utilized to screen DEGs between the AD patients and control samples.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38692009", "kind": "science-record", "revision": 4, "content_hash": "sha256:353a2dcb194860fece148cd4075d04727067dbc3a99c3a986137c03743444ada", "created_at": "2026-11-01T19:20:39Z", "updated_at": "2026-11-01T22:54:14Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "The mechanism of mitochondrial metabolic gene PMAIP1 involved in Alzheimer's disease process based on bioinformatics analysis and experimental validation.", "doi": "10.1016/j.clinsp.2024.100373", "pmid": "38692009", "authors": ["Yingchun Ling", "Lingmin Hu", "Jie Chen", "Mingyong Zhao", "Xinyang Dai"], "journal": "Clinics (Sao Paulo, Brazil)", "year": 2024, "abstract": "OBJECTIVES: This study explored novel biomarkers that can affect the diagnosis and treatment in Alzheimer's Disease (AD) related to mitochondrial metabolism.\nMETHODS: The authors obtained the brain tissue datasets for AD from the Gene Expression Omnibus (GEO) and downloaded the mitochondrial metabolism-related genes set from MitoCarta 3.0 for analysis. 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"}]}