miR-224, miR-147b and miR-31 associated with lymph node metastasis and prognosis for lung adenocarcinoma by regulating PRPF4B, WDR82 or NR3C2.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33282547", "kind": "science-record", "revision": 7, "content_hash": "sha256:56d731a5d82068344529ee3b1adb9bd7c27fc299c013354396dad401ff3e788c", "created_at": "2026-11-01T15:41:18Z", "updated_at": "2026-11-01T22:02:39Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "miR-224, miR-147b and miR-31 associated with lymph node metastasis and prognosis for lung adenocarcinoma by regulating PRPF4B, WDR82 or NR3C2.", "doi": "10.7717/peerj.9704", "pmid": "33282547", "authors": ["Yan Wang", "Shengtao Shang", "Kun Yu", "Hongbin Sun", "Wenduan Ma", "Wei Zhao"], "journal": "PeerJ", "year": 2020, "abstract": "BACKGROUND: The present study is to screen lymph node metastasis-related microRNAs (miRNAs) in lung adenocarcinoma (LUAD) and uncover their underlying mechanisms.\nMETHODS: The miRNA microarray dataset was collected from the Gene Expression Omnibus database under accession number GSE64859. The differentially expressed miRNAs (DEMs) were identified using a t-test. Target genes of DEMs were predicted through the miRWalk2.0 database. The function of these target genes was annotated with the clusterProfiler and the Database for Annotation, Visualization and Integrated Discovery (DAVID) tools. Protein-protein interaction network was established using the STRING database to extract hub target genes. The expressions and associations with survival and lymph node metastasis of miRNAs and target genes were validated by analysis of The Cancer Genome Atlas (TCGA) dataset.\nRESULTS: Eight DEMs were identified between lymph node metastasis and non-metastasis samples of GSE64859 dataset. miRNA-target gene pairs were predicted between six DEMs and 251 target genes (i.e. hsa-miR-224-PRPF4B, hsa-miR-147b-WDR82 and hsa-miR-31-NR3C2). The clusterProfiler analysis showed WDR82 was involved in the mRNA surveillance pathway, while the GO enrichment analysis using the DAVID database indicated PRPF4B participated in the protein phosphorylation and NR3C2 was related with the transcription, DNA-templated. WDR82 and PRPF4B may be hub genes because they could interact with others. Two DEMs (miR-31-5p and miR-31-3p) and 45 target genes (including PRPF4B and NR3C2) were significantly associated with overall survival. The expressions of miR-224 and miR-147b were validated to be upregulated, while WDR82, PRPF4B and NR3C2 were downregulated in lymph node metastasis samples of TCGA datasets compared with non-metastasis samples. Also, there were significantly negative expression correlations between miR-147b and WDR82, between miR-224 and PRPF4B, as well as between miR-31 and NR3C2 in LUAD samples.\nCONCLUSIONS: The present study identified several crucial miRNA-mRNA interaction pairs, which may provide novel explanations for the lymph node metastasis and poor prognosis for LUAD patients.", "claims": [{"id": "claim-method", "statement": "Survival curves of miRNAs and their target genes were generated using the Kaplan–Meier method, and a two-sided log-rank test was performed to assess the statistical differences in overall survival (OS) between the high-expression (>median expression level) and low-expression (≤ median expression level) groups using the survival package in R (v2.4; https://cran.r-project.org/web/packages/survival/index.html).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33282547", "locator": "sections[8] \"Survival analysis and expression validation\" paragraph 2", "quote": "Survival curves of miRNAs and their target genes were generated using the Kaplan–Meier method, and a two-sided log-rank test was performed to assess the statistical differences in overall survival (OS) between the high-expression (>median expression level) and low-expression (≤ median expression level) groups using the survival package in R (v2.4; https://cran.r-project.org/web/packages/survival/index.html)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data are available at NCBI GEO: GSE64859 and at The Cancer Genome Atlas under search term TCGA-LUAD.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33282547", "locator": "sections[21] \"Data Availability\" paragraph 2", "quote": "Data are available at NCBI GEO: GSE64859 and at The Cancer Genome Atlas under search term TCGA-LUAD."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:33282547"], "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:GSE64859"], "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:GSE64859"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33282547", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.9704", "sha256": 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"access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#table-1", "version": null, "note": "Differentially expressed miRNAs.", "structure": {"pmcid": "PMC7694553", "section_index": 10, "section_title": "Identification of DEMs", "row_count": 9, "column_count": 4}, "table": {"label": "Table 1", "caption": "Differentially expressed miRNAs.", "rows": [["miRNA", "logFC", "P-value", "FDR"], ["hsa-miR-3975", "5.57", "1.82E−05", "2.73E−03"], ["hsa-miR-1269a", "4.84", "2.15E−04", "1.93E−02"], ["hsa-miR-31-3p", "4.76", "1.65E−04", "1.86E−02"], ["hsa-miR-224-5p", "4.40", "3.46E−04", "2.59E−02"], ["hsa-miR-147b", "4.29", "4.58E−04", "2.94E−02"], ["hsa-miR-31-5p", "4.09", "7.38E−04", "4.14E−02"], ["hsa-miR-371b-5p", "−7.37", "1.37E−05", "2.73E−03"], ["hsa-miR-371a-3p", "−7.37", "1.37E−05", "2.73E−03"]], "row_count": 9, "column_count": 4, "numeric_cells": 32, "header_rows": 1, "locator": "section[10]/table-wrap[1]#table-1"}}, {"id": "asset:table:pmid:33282547:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:3c4e84ac8d3a576f486cb3f0318d36b43d09c547faa1a43605754889e4013623", "bytes": 2962, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#table-2", "version": null, "note": "KEGG enrichment for the genes of differentially expressed miRNAs.", "structure": {"pmcid": "PMC7694553", "section_index": 12, "section_title": "Function enrichment for the target genes in the miRNA regulatory network", "row_count": 34, "column_count": 5}, "table": {"label": "Table 2", "caption": "KEGG enrichment for the genes of differentially expressed miRNAs.", "rows": [["miRNA", "ID", "Description", "Adjusted p-value", "Gene ID"], ["hsa-miR-1269a", "hsa04919", "Thyroid hormone signaling pathway", "3.60E−04", "CCND1/FOXO1/SLC16A2"], ["hsa-miR-1269a", "hsa05215", "Prostate cancer", "6.18E−03", "CCND1/FOXO1"], ["hsa-miR-1269a", "hsa04933", "AGE-RAGE signaling pathway in diabetic complications", "6.56E−03", "CCND1/FOXO1"], ["hsa-miR-1269a", "hsa05165", "Human papillomavirus infection", "6.78E−034", "CCND1/FOXO1/PTGER4"], ["hsa-miR-1269a", "hsa04152", "AMPK signaling pathway", "9.33E−03", "CCND1/FOXO1"], ["hsa-miR-1269a", "hsa04068", "FoxO signaling pathway", "3.60E−02", "CCND1/FOXO1"], ["hsa-miR-1269a", "hsa04371", "Apelin signaling pathway", "1.20E−02", "CCND1/MEF2D"], ["hsa-miR-1269a", "hsa04218", "Cellular senescence", "1.62E−02", "CCND1/FOXO1"], ["hsa-miR-1269a", "hsa00120", "Primary bile acid biosynthesis", "2.11E−02", "CYP7B1"], ["hsa-miR-1269a", "hsa05163", "Human cytomegalovirus infection", "3.07E−02", "CCND1/PTGER4"], ["hsa-miR-1269a", "hsa05216", "Thyroid cancer", "4.54E−02", "CCND1"], ["hsa-miR-147b", "hsa03015", "mRNA surveillance pathway", "4.49E−02", "WDR82"], ["hsa-miR-224-5p", "hsa04310", "Wnt signaling pathway", "1.28E−03", "CAMK2D/GSK3B/LRP6/ MAP3K7/FZD4"], ["hsa-miR-31-3p", "hsa05033", "Nicotine addiction", "1.00E−02", "GRIN2A"], ["hsa-miR-31-3p", "hsa05030", "Cocaine addiction", "1.22E−02", "GRIN2A"], ["hsa-miR-31-3p", "hsa05014", "Amyotrophic lateral sclerosis (ALS)", "1.42E−02", "GRIN2A"], ["hsa-miR-31-3p", "hsa04720", "Long-term potentiation", "1.67E−02", "GRIN2A"], ["hsa-miR-31-3p", "hsa05031", "Amphetamine addiction", "1.72E−02", "GRIN2A"], ["hsa-miR-31-3p", "hsa05211", "Renal cell carcinoma", "1.72E−02", "ELOC"], ["hsa-miR-31-3p", "hsa04713", "Circadian entrainment", "2.42E−02", "GRIN2A"], ["hsa-miR-31-3p", "hsa05017", "Spinocerebellar ataxia", "2.44E−02", "GRIN2A"], ["hsa-miR-31-3p", "hsa04066", "HIF-1 signaling pathway", "2.71E−02", "ELOC"], ["hsa-miR-31-3p", "hsa04724", "Glutamatergic synapse", "2.84E−02", "GRIN2A"], ["hsa-miR-31-3p", "hsa04728", "Dopaminergic synapse", "3.26E−02", "GRIN2A"], ["hsa-miR-31-3p", "hsa05322", "Systemic lupus erythematosus", "3.30E−02", "GRIN2A"], ["hsa-miR-31-3p", "hsa04120", "Ubiquitin mediated proteolysis", "3.38E−02", "ELOC"], ["hsa-miR-31-3p", "hsa05010", "Alzheimer disease", "4.24E−02", "GRIN2A"], ["hsa-miR-31-3p", "hsa05034", "Alcoholism", "4.56E−02", "GRIN2A"], ["hsa-miR-31-3p", "hsa04020", "Calcium signaling pathway", "4.78E−02", "GRIN2A"], ["hsa-miR-31-5p", "hsa04360", "Axon guidance", "9.68E−04", "FZD3/CAMK2D/PLXNA2/ PPP3CA/RASA1/PLXNA4"], ["hsa-miR-371a-3p", "hsa00513", "Various types of N-glycan biosynthesis", "1.94E−02", "MAN2A2"], ["hsa-miR-371a-3p", "hsa00510", "N-Glycan biosynthesis", "2.48E−02", "MAN2A2"], ["hsa-miR-371a-3p", "hsa03015", "mRNA surveillance pathway", "4.49E−02", "DAZAP1"]], "row_count": 34, "column_count": 5, "numeric_cells": 102, "header_rows": 1, "locator": "section[12]/table-wrap[1]#table-2"}}], "gaps": ["asset:data:geo:GSE64859 not downloaded", "asset:data:geo:GSE64859 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["logrank_test"], "assets": ["source:pmid:33282547", "data:geo:GSE64859", "asset:table:pmid:33282547:1", "asset:table:pmid:33282547:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE64859"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:24:47Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 31928, "completion_tokens": 1589, "cached_tokens": 784}}, "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:33282547", "type": "paper", "label": "pmid:33282547"}, {"id": "source:pmid:33282547", "type": "manuscript", "label": "PMID 33282547 full text"}, {"id": "data:geo:GSE64859", "type": "dataset", "label": "GEO GSE64859"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33282547", "type": "paper", "label": "pmid:33282547"}, {"id": "source:pmid:33282547", "type": "manuscript", "label": "PMID 33282547 full text"}, {"id": "data:geo:GSE64859", "type": "dataset", "label": "GEO GSE64859"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33282547", "type": "extraction", "used": ["source:pmid:33282547"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE64859", "type": "accession_resolution", "used": ["data:geo:GSE64859"], "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:33282547", "parent_hash": "sha256:8c424d00407dbe771f4a5ab1e50f1777c1808a63c647374b601fa68b52416283", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE64859 licence not read", "asset:data:geo:GSE64859 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ir underlying mechanisms. 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