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pmid:36544657

MiR-148a-3p attenuates apoptosis and inflammation by targeting CNTN4 in atherosclerosis.

Kai Wang · Xi-Tong Huang · Yan-Ping Miao · Xiao-Long Bai · Feng Jin

Annals of translational medicine · 2022 doi:10.21037/atm-22-3768

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:36544657
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2026-11-01T19:01:04Z
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paper object · 10 fields
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title
MiR-148a-3p attenuates apoptosis and inflammation by targeting CNTN4 in atherosclerosis.
doi
10.21037/atm-22-3768
pmid
36544657
authors array · 5 items
[0]
Kai Wang
[1]
Xi-Tong Huang
[2]
Yan-Ping Miao
[3]
Xiao-Long Bai
[4]
Feng Jin
journal
Annals of translational medicine
year
2022
abstract
Background: Atherosclerosis (AS) seriously affects human health. The role of microRNAs (miRNAs) in the pathogenesis and progression of AS has become a focus of research. Our goal was to identify the biological effect of differentially expressed miRNAs (DE-miRNAs) in AS. Methods: To analyze differentially expressed genes (DEGs), including differentially expressed mRNAs (DE-mRNAs) and DE-miRNAs, in AS by using the Gene Expression Omnibus (GEO) database and limma package. DEGs protein-protein interaction (PPI) network and functional enrichment analysis were constructed by using the search tool for the retrieval of interacting genes/proteins (STRING) database, Cytoscape software and Cytoscape plugin "ClueGO2.5.6". We established a coexpression network of dysregulated miRNAs and mRNAs to predict the function of miRNAs by using miRWalk database and Pearson correlation coefficient (PCC) analysis. Cellular experiments were used to validate the results of bioinformatics. Results: First, 69 common DEGs were obtained from datasets GSE43292 and GSE97210 using the limma package in R. Next, a DEG PPI network was constructed. Functional enrichment analysis of DEGs showed that 11 functional pathways were significantly enriched, such as positive regulation of monocyte chemotaxis. Seven common DE-miRNAs were obtained from the GSE99685 dataset and DE-mRNAs predicted miRNAs through the miRWalk database. The miRNA-mRNA network constructed using Cytoscape software suggested that miR-148a-3p targeted contactin 4 (CNTN4). Quantitative real-time polymerase chain reaction (qRT-PCR) assay results indicated that miR-148a-3p was downregulated and CNTN4 was upregulated in the THP-1 + phorbol 12-myristate 13-acetate (PMA) + oxidized low-density lipoprotein (oxLDL) group compared with the THP-1 + PMA group. qRT-PCR, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) found that upregulated miR-148a-3p significantly inhibited the expression of CNTN4, cell apoptosis, and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) concentrations in oxLDL-induced THP-1 macrophages. In addition, a dual-luciferase reporter assay demonstrated that CNTN4 was a target gene of miR-148a-3p. Conclusions: Overall, these findings suggested that miR-148a-3p inhibited oxLDL-induced cell apoptosis and inflammation via targeting CNTN4 in THP-1 macrophages.
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The limma package in R was used to find DEGs in AS compared with normal samples (12).
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MiR-148a-3p attenuates apoptosis and inflammation by targeting CNTN4 in ather
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assay:4
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36544657", "kind": "science-record", "revision": 4, "content_hash": "sha256:94d7d4c42cd97252aa64b666e79e634ae4c14a8a2e44edc9b68bd884dd59525e", "created_at": "2026-11-01T19:01:04Z", "updated_at": "2026-11-01T22:50:53Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "MiR-148a-3p attenuates apoptosis and inflammation by targeting CNTN4 in atherosclerosis.", "doi": "10.21037/atm-22-3768", "pmid": "36544657", "authors": ["Kai Wang", "Xi-Tong Huang", "Yan-Ping Miao", "Xiao-Long Bai", "Feng Jin"], "journal": "Annals of translational medicine", "year": 2022, "abstract": "Background: Atherosclerosis (AS) seriously affects human health. The role of microRNAs (miRNAs) in the pathogenesis and progression of AS has become a focus of research. Our goal was to identify the biological effect of differentially expressed miRNAs (DE-miRNAs) in AS.\nMethods: To analyze differentially expressed genes (DEGs), including differentially expressed mRNAs (DE-mRNAs) and DE-miRNAs, in AS by using the Gene Expression Omnibus (GEO) database and limma package. DEGs protein-protein interaction (PPI) network and functional enrichment analysis were constructed by using the search tool for the retrieval of interacting genes/proteins (STRING) database, Cytoscape software and Cytoscape plugin \"ClueGO2.5.6\". We established a coexpression network of dysregulated miRNAs and mRNAs to predict the function of miRNAs by using miRWalk database and Pearson correlation coefficient (PCC) analysis. Cellular experiments were used to validate the results of bioinformatics.\nResults: First, 69 common DEGs were obtained from datasets GSE43292 and GSE97210 using the limma package in R. Next, a DEG PPI network was constructed. Functional enrichment analysis of DEGs showed that 11 functional pathways were significantly enriched, such as positive regulation of monocyte chemotaxis. Seven common DE-miRNAs were obtained from the GSE99685 dataset and DE-mRNAs predicted miRNAs through the miRWalk database. The miRNA-mRNA network constructed using Cytoscape software suggested that miR-148a-3p targeted contactin 4 (CNTN4). Quantitative real-time polymerase chain reaction (qRT-PCR) assay results indicated that miR-148a-3p was downregulated and CNTN4 was upregulated in the THP-1 + phorbol 12-myristate 13-acetate (PMA) + oxidized low-density lipoprotein (oxLDL) group compared with the THP-1 + PMA group. qRT-PCR, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) found that upregulated miR-148a-3p significantly inhibited the expression of CNTN4, cell apoptosis, and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) concentrations in oxLDL-induced THP-1 macrophages. In addition, a dual-luciferase reporter assay demonstrated that CNTN4 was a target gene of miR-148a-3p.\nConclusions: Overall, these findings suggested that miR-148a-3p inhibited oxLDL-induced cell apoptosis and inflammation via targeting CNTN4 in THP-1 macrophages.", "claims": [{"id": "claim-method", "statement": "The limma package in R was used to find DEGs in AS compared with normal samples (12).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36544657", "locator": "sections[4] \"DEGs between AS and normal tissue\" paragraph 2", "quote": "The limma package in R was used to find DEGs in AS compared with normal samples (12)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data Sharing Statement: Available at https://atm.amegroups.com/article/view/10.21037/atm-22-3768/dss", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36544657", "locator": "sections[24] \"fn-group\" paragraph 1", "quote": "Data Sharing Statement: Available at https://atm.amegroups.com/article/view/10.21037/atm-22-3768/dss"}], "state": "complete"}, {"id": "claim-target-result", "statement": "First, 69 common DEGs were obtained from datasets GSE43292 and GSE97210 using the limma package in R.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36544657", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "First, 69 common DEGs were obtained from datasets GSE43292 and GSE97210 using the limma package in R."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "First, 69 common DEGs were obtained from datasets GSE43292 and GSE97210 using the limma package in R.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36544657"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE43292"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE43292"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36544657", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21037/atm-22-3768", "sha256": 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"structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Data Sharing Statement: Available at https://atm.amegroups.com/article/view/10.21037/atm-22-3768/dss", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2559712", "GSM2559713", "GSM2559714", "GSM2559715", "GSM2559716", "GSM2559717"], "sample_count": 6, "group_sizes": null, "group_sizes_basis": null, "platform": "16956", "taxon": "Homo sapiens", "title": "LncRNA/mRNA expression profiling for human normal arterial intimae and advanced atherosclerotic plaques", "resolution_checked_at": "2026-11-01T18:06:44Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE99685", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE99685", "sha256": null, "bytes": null, 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false}}], "gaps": ["asset:data:geo:GSE43292 not downloaded", "asset:data:geo:GSE43292 licence not read", "asset:data:geo:GSE97210 not downloaded", "asset:data:geo:GSE97210 licence not read", "asset:data:geo:GSE99685 not downloaded", "asset:data:geo:GSE99685 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The limma package in R was used to find DEGs in AS compared with normal samples (12)."}}, {"id": "method-2", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], 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pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "pathway enrichment"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["normalise_counts", 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE43292", "GSE97210", "GSE99685"], "resolved_accessions": ["GSE43292", "GSE97210", "GSE99685"], "statements": ["Data Sharing Statement: Available at https://atm.amegroups.com/article/view/10.21037/atm-22-3768/dss"], "basis": "The paper names GSE43292, GSE97210, GSE99685 in Gene Expression Omnibus (GEO) database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:36544657", "data:geo:GSE43292"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE43292"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:20:25Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 8101, "completion_tokens": 1288, "cached_tokens": 256}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", 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