MIR222HG attenuates macrophage M2 polarization and allergic inflammation in allergic rhinitis by targeting the miR146a-5p/TRAF6/NF-κB axis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37205104", "kind": "science-record", "revision": 4, "content_hash": "sha256:42bc8f4b28cd42375ca5469841c083c9e164900259796f5c281b923bfb27e37b", "created_at": "2026-11-01T19:01:54Z", "updated_at": "2026-11-01T22:51:56Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "MIR222HG attenuates macrophage M2 polarization and allergic inflammation in allergic rhinitis by targeting the miR146a-5p/TRAF6/NF-κB axis.", "doi": "10.3389/fimmu.2023.1168920", "pmid": "37205104", "authors": ["Silu Wen", "Fen Li", "Yulei Tang", "Lin Dong", "Yan He", "Yuqin Deng", "Zezhang Tao"], "journal": "Frontiers in immunology", "year": 2023, "abstract": "Although M2 macrophages are involved in the orchestration of type 2 inflammation in allergic diseases, the mechanisms underlying non-coding RNA (ncRNA)-mediated macrophage polarization in allergic rhinitis (AR) have not been systematically understood. Here, we identified long non-coding RNA (lncRNA) MIR222HG as a key regulator of macrophage polarization and revealed its role in AR. Consistent with our bioinformatic analysis of GSE165934 dataset derived from the Gene Expression Omnibus (GEO) database, lncRNA-MIR222HG and murine mir222hg were downregulated in our clinical samples and animal models of AR, respectively. Mir222hg was upregulated in M1 macrophages and downregulated in M2 macrophages. The allergen-ovalbumin facilitated polarization of RAW264.7 cells to the M2 phenotype, accompanied by the downregulation of mir222hg expression in a dose-dependent manner. Mir222hg facilitates macrophage M1 polarization and reverses M2 polarization caused by ovalbumin. Furthermore, mir222hg attenuates macrophage M2 polarization and allergic inflammation in the AR mouse model. Mechanistically, a series of gain- and loss-of-function experiments and rescue experiments were performed to verify the role of mir222hg as a ceRNA sponge that adsorbed miR146a-5p, upregulated Traf6, and activated the IKK/IκB/P65 pathway. Collectively, the data highlight the remarkable role of MIR222HG in the modulation of macrophage polarization and allergic inflammation, as well as its potential role as a novel AR biomarker or therapeutic target.", "claims": [{"id": "claim-method", "statement": "Statistical significance was assessed by Mann–Whitney U test or unpaired t-test for experiments comparing two groups appropriately, whereas two-way ANOVA followed by Sidak’s multiple comparisons test was used for comparisons between more than two groups, and the linear correlation between the transcript-levels of MIR222HG and macrophage inflammation-related genes involved in this study was drawn by using Spearman rank correlation.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37205104", "locator": "sections[17] \"Statistical analyses\" paragraph 2", "quote": "Statistical significance was assessed by Mann–Whitney U test or unpaired t-test for experiments comparing two groups appropriately, whereas two-way ANOVA followed by Sidak’s multiple comparisons test was used for comparisons between more than two groups, and the linear correlation between the transcript-levels of MIR222HG and macrophage inflammation-related genes involved in this study was drawn by using Spearman rank correlation."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37205104", "locator": "sections[29] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Mechanistically, a series of gain- and loss-of-function experiments and rescue experiments were performed to verify the role of mir222hg as a ceRNA sponge that adsorbed miR146a-5p, upregulated Traf6, and activated the IKK/IκB/P65 pathway.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37205104", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Mechanistically, a series of gain- and loss-of-function experiments and rescue experiments were performed to verify the role of mir222hg as a ceRNA sponge that adsorbed miR146a-5p, upregulated Traf6, and activated the IKK/IκB/P65 pathway."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Mechanistically, a series of gain- and loss-of-function experiments and rescue experiments were performed to verify the role of mir222hg as a ceRNA sponge that adsorbed miR146a-5p, upregulated Traf6, and activated the IKK/IκB/P65 pathway.", "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:37205104"], "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:GSE165934"], "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:GSE165934"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37205104", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2023.1168920", "sha256": "sha256:e2055f4572917c0c92ca60e3c43403b0080dae0fd23b5bfaad34755e7bd9f2df", "bytes": 64757, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2023.1168920", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10185836", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE165934", "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=GSE165934", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE165934", "version": null, "note": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM5058526", "GSM5058527", "GSM5058528", "GSM5058529", "GSM5058530", "GSM5058531", "GSM5058532", "GSM5058533", "GSM5058534", "GSM5058535", "GSM5058536", "GSM5058537", "GSM5058538", "GSM5058539", "GSM5058540", "GSM5058541", "GSM5058542", "GSM5058543", "GSM5058544"], "sample_count": 19, "group_sizes": null, "group_sizes_basis": null, "platform": "23126", "taxon": "Homo sapiens", "title": "Expression data from peripheral blood mononuclear cells(PBMCs) of patients with bronchial asthma and normal controls", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE165934 not downloaded", "asset:data:geo:GSE165934 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Statistical significance was assessed by Mann–Whitney U test or unpaired t-test for experiments comparing two groups appropriately, whereas two-way ANOVA followed by Sidak’s multiple comparisons test was used for comparisons between more than two groups, and the linear correlation between the transcript-levels of MIR222HG and macrophage inflammation-related genes involved in this study was drawn by using Spearman rank correlation."}}, {"id": "method-2", "family": "correlation_analysis", "specific": "spearman", "label": "Correlation analysis", "dsl_operations": ["spearman_rho"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Spearman rank correlation"}}], "targets": [], "gaps": []}, "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": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: anova."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE165934"], "resolved_accessions": ["GSE165934"], "statements": ["The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors."], "basis": "The paper names GSE165934 in NCBI Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "assets": ["source:pmid:37205104", "data:geo:GSE165934"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE165934"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:40:47Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 17651, "completion_tokens": 1591, "cached_tokens": 264}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:37205104", "type": "paper", "label": "pmid:37205104"}, {"id": "source:pmid:37205104", "type": "manuscript", "label": "PMID 37205104 full text"}, {"id": "data:geo:GSE165934", "type": "dataset", "label": "GEO GSE165934"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37205104", "type": "paper", "label": "pmid:37205104"}, {"id": "source:pmid:37205104", "type": "manuscript", "label": "PMID 37205104 full text"}, {"id": "data:geo:GSE165934", "type": "dataset", "label": "GEO GSE165934"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37205104", "type": "extraction", "used": ["source:pmid:37205104"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE165934", "type": "accession_resolution", "used": ["data:geo:GSE165934"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:37205104", "parent_hash": "sha256:42474cfbecc1ad21c803525c0ed05bf4a6f08f816a0c37186dc5822635f23434", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE165934 licence not read", "asset:data:geo:GSE165934 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": ["Omnibus (GEO) database, lncRNA-MIR222HG and murine mir222hg were downregulated in our clinical", "rization and allergic inflammation in the AR mouse model. Mechanistically, a series of gain- and loss", "rization and allergic inflammation in the AR mouse model. Mechanistically, a series of gain- an", "was established as previously reported (27). Mice were randomly divided into two groups, i.e., cont"], "order_basis": "paper_text_order:622", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ai, China). RAW264.7, and HEK293T cells were cultured in Dulbecco’s modified Eagle medium-high glucos", "sphere of 5% CO2 and 95% air (30). THP-1 was cultured in RPMI-1640 medium (HyClone, UT, USA), supplem"], "order_basis": "paper_text_order:4795", "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": ["xperiments in the present study. Control and transfected RAW264.7 cells were induced to the M1 macrop"], "order_basis": "paper_text_order:5265", "id": "assay:3"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Statistical significance was assessed by Mann–Whitney U test or unpaired t-test for experiments comparing two groups appropriately, whereas two-way ANOVA followed by Sidak’s multiple comparisons test was used for comparisons between more than two groups, and the linear correlation between the transcript-levels of MIR222HG and macrophage inflammation-related genes involved in this study was drawn by using Spearman rank correlation."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}