An integrated analysis of the competing endogenous RNA network and co-expression network revealed seven hub long non-coding RNAs in osteoarthritis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32435461", "kind": "science-record", "revision": 9, "content_hash": "sha256:a372ab4a1f6ecfd2e74b9c87d7d7415a9c41bae568dccf601a945dc943144cc7", "created_at": "2026-11-01T15:41:02Z", "updated_at": "2026-11-01T22:44:53Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "An integrated analysis of the competing endogenous RNA network and co-expression network revealed seven hub long non-coding RNAs in osteoarthritis.", "doi": "10.1302/2046-3758.93.BJR-2019-0140.R2", "pmid": "32435461", "authors": ["Haitao Chen", "Liaobin Chen"], "journal": "Bone & joint research", "year": 2020, "abstract": "AIMS: This study aimed to uncover the hub long non-coding RNAs (lncRNAs) differentially expressed in osteoarthritis (OA) cartilage using an integrated analysis of the competing endogenous RNA (ceRNA) network and co-expression network.\nMETHODS: Expression profiles data of ten OA and ten normal tissues of human knee cartilage were obtained from the Gene Expression Omnibus (GEO) database (GSE114007). The differentially expressed messenger RNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified using the edgeR package. We integrated human microRNA (miRNA)-lncRNA/mRNA interactions with DElncRNA/DEmRNA expression profiles to construct a ceRNA network. Likewise, lncRNA and mRNA expression profiles were used to build a co-expression network with the WGCNA package. Potential hub lncRNAs were identified based on an integrated analysis of the ceRNA network and co-expression network. StarBase and Multi Experiment Matrix databases were used to verify the lncRNAs.\nRESULTS: We detected 1,212 DEmRNAs and 49 DElncRNAs in OA and normal knee cartilage. A total of 75 dysregulated lncRNA-miRNA interactions and 711 dysregulated miRNA-mRNA interactions were obtained in the ceRNA network, including ten DElncRNAs, 69 miRNAs, and 72 DEmRNAs. Similarly, 1,330 dysregulated lncRNA-mRNA interactions were used to construct the co-expression network, which included ten lncRNAs and 407 mRNAs. We finally identified seven hub lncRNAs, named MIR210HG, HCP5, LINC00313, LINC00654, LINC00839, TBC1D3P1-DHX40P1, and ISM1-AS1. Subsequent enrichment analysis elucidated that these lncRNAs regulated extracellular matrix organization and enriched in osteoclast differentiation, the FoxO signalling pathway, and the tumour necrosis factor (TNF) signalling pathway in the development of OA.\nCONCLUSION: The integrated analysis of the ceRNA network and co-expression network identified seven hub lncRNAs associated with OA. These lncRNAs may regulate extracellular matrix changes and chondrocyte homeostasis in OA progress.Cite this article: Bone Joint Res. 2020;9(3):90-98.", "claims": [{"id": "claim-method", "statement": "We used estimateCommonDisp() and estimateTagwiseDisp() function for estimating the dispersion, and exactTest() function for tagwise tests using the exact negative binomial test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32435461", "locator": "sections[7] \"Differential analysis of lncRNAs and mRNAs\" paragraph 2", "quote": "We used estimateCommonDisp() and estimateTagwiseDisp() function for estimating the dispersion, and exactTest() function for tagwise tests using the exact negative binomial test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Total RNA-seq datasets of human knee cartilage were obtained from the Gene Expression Omnibus (GEO) database (GSE114007). Expression profiles data of ten OA and ten normal knee samples were based on platform GPL18573 (NextSeq 500 System; Illumina, San Diego, California, USA).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32435461", "locator": "sections[6] \"Data collection and preprocessing\" paragraph 2", "quote": "Total RNA-seq datasets of human knee cartilage were obtained from the Gene Expression Omnibus (GEO) database (GSE114007). Expression profiles data of ten OA and ten normal knee samples were based on platform GPL18573 (NextSeq 500 System; Illumina, San Diego, California, USA)."}], "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:32435461"], "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:GSE114007"], "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:GSE114007"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32435461", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1302/2046-3758.93.BJR-2019-0140.R2", "sha256": "sha256:9b30f360f065b7f3ea7722fc67627fe431bb6516f9652a03242a9c5045b698aa", "bytes": 31182, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1302/2046-3758.93.BJR-2019-0140.R2", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7229307", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE114007", "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=GSE114007", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE114007", "version": null, "note": "Total RNA-seq datasets of human knee cartilage were obtained from the Gene Expression Omnibus (GEO) database (GSE114007). Expression profiles data of ten OA and ten normal knee samples were based on platform GPL18573 (NextSeq 500 System; Illumina, San Diego, California, USA).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Total RNA-seq datasets of human knee cartilage were obtained from the Gene Expression Omnibus (GEO) database (GSE114007). Expression profiles data of ten OA and ten normal knee samples were based on platform GPL18573 (NextSeq 500 System; Illumina, San Diego, California, USA).", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM3130531", "GSM3130532", "GSM3130533", "GSM3130534", "GSM3130535", "GSM3130536", "GSM3130537", "GSM3130538", "GSM3130539", "GSM3130540", "GSM3130541", "GSM3130542", "GSM3130543", "GSM3130544", "GSM3130545", "GSM3130546", "GSM3130547", "GSM3130548", "GSM3130549", "GSM3130550", "GSM3130551", "GSM3130552", "GSM3130553", "GSM3130554", "GSM3130555", "GSM3130556", "GSM3130557", "GSM3130558", "GSM3130559", "GSM3130560", "GSM3130561", "GSM3130562", "GSM3130563", "GSM3130564", "GSM3130565", "GSM3130566", "GSM3130567", "GSM3130568"], "sample_count": 38, "group_sizes": null, "group_sizes_basis": null, "platform": "11154;18573", "taxon": "Homo sapiens", "title": "Identification of transcription factors responsible for dysregulated networks in human osteoarthritis cartilage by global gene expression analysis", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:32435461:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:f03b19721be238bb519af044c592bab9bb64e1aea01a3e6bc6a564bfe4d8bc3f", "bytes": 1237, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#table1-2046-3758.93.BJR-2019-0140.R2", "version": null, "note": "The top ten up-regulated and down-regulated long non-coding RNAs", "structure": {"pmcid": "PMC7229307", "section_index": 13, "section_title": "DElncRNAs in osteoarthritis and normal knee samples", "row_count": 21, "column_count": 5}, "table": {"label": "Table I.", "caption": "The top ten up-regulated and down-regulated long non-coding RNAs", "rows": [["Type", "lncRNA", "logFC", "p-value*", "FDR"], ["Up-regulated", "LINC00654", "1.72", "< 0.001", "1.47E-11"], ["", "ISM1-AS1", "2.61", "< 0.001", "3.52E-10"], ["", "FAM225A", "2.72", "< 0.001", "2.13E-07"], ["", "LNX1-AS1", "2.48", "< 0.001", "3.85E-07"], ["", "SLC8A1-AS1", "3.14", "< 0.001", "4.81E-06"], ["", "MIR31HG", "2.15", "< 0.001", "2.65E-05"], ["", "MAGI2-AS2", "2.88", "< 0.001", "1.14E-04"], ["", "CELF2-AS2", "1.94", "< 0.001", "1.14E-04"], ["", "LINC00839", "2.57", "< 0.001", "1.94E-04"], ["", "ABCC5-AS1", "3.15", "< 0.001", "4.61E-04"], ["Down-regulated", "AL360012.1", "−2.74", "< 0.001", "1.81E-13"], ["", "Z93241.1", "−2.73", "< 0.001", "3.40E-12"], ["", "ILF3-DT", "−1.56", "< 0.001", "3.52E-10"], ["", "MATN1-AS1", "−2.52", "< 0.001", "1.41E-09"], ["", "MIR210HG", "−1.66", "< 0.001", "4.72E-08"], ["", "SMG7-AS1", "−2.09", "< 0.001", "1.36E-07"], ["", "AFDN-DT", "−2.20", "< 0.001", "2.13E-07"], ["", "PROSER2-AS1", "−1.62", "< 0.001", "2.49E-07"], ["", "LINC00167", "−1.82", "< 0.001", "3.19E-07"], ["", "TOB1-AS1", "−2.27", "< 0.001", "1.41E-06"]], "row_count": 21, "column_count": 5, "numeric_cells": 68, "header_rows": 1, "locator": "section[13]/table-wrap[1]#table1-2046-3758.93.BJR-2019-0140.R2"}}, {"id": "asset:table:pmid:32435461:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:6684afbd71a5939c0b53af8bdae17f2e547e6bc40910f6c0a2a62612f3f1850b", "bytes": 1151, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[1]#table2-2046-3758.93.BJR-2019-0140.R2", "version": null, "note": "The top ten up-regulated and down-regulated messenger RNAs", "structure": {"pmcid": "PMC7229307", "section_index": 14, "section_title": "DEmRNAs in osteoarthritis and normal samples", "row_count": 21, "column_count": 5}, "table": {"label": "Table II.", "caption": "The top ten up-regulated and down-regulated messenger RNAs", "rows": [["Type", "mRNA", "logFC", "p-value*", "FDR"], ["Up-regulated", "TYMP", "2.52", "< 0.001", "6.78E-26"], ["", "ASPM", "5.15", "< 0.001", "1.07E-16"], ["", "PREX2", "2.89", "< 0.001", "1.99E-16"], ["", "SKP2", "1.69", "< 0.001", "1.59E-15"], ["", "CFI", "3.40", "< 0.001", "1.74E-15"], ["", "HMGA2", "4.17", "< 0.001", "2.07E-15"], ["", "KCNN4", "2.87", "< 0.001", "1.03E-14"], ["", "TTC9", "2.59", "< 0.001", "1.90E-14"], ["", "THBS2", "2.83", "< 0.001", "1.59E-13"], ["", "ST6GALNAC5", "4.24", "< 0.001", "2.54E-13"], ["Down-regulated", "DDIT3", "−3.00", "< 0.001", "8.00E-42"], ["", "IER2", "−3.04", "< 0.001", "8.06E-41"], ["", "MAFF", "−3.45", "< 0.001", "1.34E-39"], ["", "PIGA", "−2.46", "< 0.001", "6.58E-38"], ["", "JUN", "−3.53", "< 0.001", "1.87E-29"], ["", "RARA", "−2.42", "< 0.001", "2.05E-26"], ["", "CISH", "−3.35", "< 0.001", "2.05E-26"], ["", "PIM2", "−2.80", "< 0.001", "2.05E-26"], ["", "OTUD1", "−2.37", "< 0.001", "2.61E-26"], ["", "KLF10", "−2.37", "< 0.001", "6.80E-25"]], "row_count": 21, "column_count": 5, "numeric_cells": 61, "header_rows": 1, "locator": "section[14]/table-wrap[1]#table2-2046-3758.93.BJR-2019-0140.R2"}}, {"id": "asset:table:pmid:32435461:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b8434abf3e7207a3b3c6e0cf905650e88642a5d24073ae186ecae84f91d2f70a", "bytes": 1034, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[18]/table-wrap[1]#table3-2046-3758.93.BJR-2019-0140.R2", "version": null, "note": "Top five terms of Kyoto Encyclopedia of Genes and Genomes analysis", "structure": {"pmcid": "PMC7229307", "section_index": 18, "section_title": "Functional enrichment analysis", "row_count": 6, "column_count": 6}, "table": {"label": "Table III.", "caption": "Top five terms of Kyoto Encyclopedia of Genes and Genomes analysis", "rows": [["ID", "Description", "GeneRatio", "Count", "FDR", "Genes"], ["hsa04380", "Osteoclast differentiation", "0.074", "14", "0.0003", "BTK, FCGR3A, FOS, FOSB, FOSL2, JUN, JUNB, JUND, NFKB2, NFKBIA, SOCS1, SOCS3, SPI1, TYROBP"], ["hsa04068", "FoxO signalling pathway", "0.074", "14", "0.0003", "BCL6, BNIP3, CCND1, CCNG2, CDKN1A, CDKN1B, GADD45A, GADD45B, IRS2, KLF2, PLK2, PLK3, SKP2, SOD2"], ["hsa04668", "TNF signalling pathway", "0.063", "12", "0.0006", "BCL3, CEBPB, FOS, ICAM1, IRF1, JUN, JUNB, NFKBIA, NOD2, PTGS2, SOCS3, TNFRSF1B"], ["hsa05222", "Small cell lung cancer", "0.058", "11", "0.0006", "CCND1, CDK6, CDKN1A, CDKN1B, CYCS, FN1, GADD45A, GADD45B, NFKBIA, PTGS2, SKP2"], ["hsa04115", "p53 signalling pathway", "0.053", "10", "0.0006", "CCND1, CCNG2, CDK1, CDK6, CDKN1A, CYCS, GADD45A, GADD45B, RRM2, SESN2"]], "row_count": 6, "column_count": 6, "numeric_cells": 24, "header_rows": 1, "locator": "section[18]/table-wrap[1]#table3-2046-3758.93.BJR-2019-0140.R2"}}], "gaps": ["asset:data:geo:GSE114007 not downloaded", "asset:data:geo:GSE114007 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "edger", "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": "We used estimateCommonDisp() and estimateTagwiseDisp() function for estimating the dispersion, and exactTest() function for tagwise tests using the exact negative binomial test."}}], "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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: edger."}, "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": ["GSE114007"], "resolved_accessions": ["GSE114007"], "statements": ["Total RNA-seq datasets of human knee cartilage were obtained from the Gene Expression Omnibus (GEO) database (GSE114007). Expression profiles data of ten OA and ten normal knee samples were based on platform GPL18573 (NextSeq 500 System; Illumina, San Diego, California, USA)."], "basis": "The paper names GSE114007 in Gene Expression Omnibus (GEO) 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:32435461", "data:geo:GSE114007", "asset:table:pmid:32435461:1", "asset:table:pmid:32435461:2", "asset:table:pmid:32435461:3"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE114007"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:19:52Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 3, "usage": {"prompt_tokens": 25227, "completion_tokens": 1046, "cached_tokens": 792}}, "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:32435461", "type": "paper", "label": "pmid:32435461"}, {"id": "source:pmid:32435461", "type": "manuscript", "label": "PMID 32435461 full text"}, {"id": "data:geo:GSE114007", "type": "dataset", "label": "GEO GSE114007"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:32435461", "type": "paper", "label": "pmid:32435461"}, {"id": "source:pmid:32435461", "type": "manuscript", "label": "PMID 32435461 full text"}, {"id": "data:geo:GSE114007", "type": "dataset", "label": "GEO GSE114007"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-32435461", "type": "extraction", "used": ["source:pmid:32435461"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE114007", "type": "accession_resolution", "used": ["data:geo:GSE114007"], "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:32435461", "parent_hash": "sha256:fa81e4e3f8fcfe929df7977f991b69625211dda360a4657fb8e048fbf4a57944", "fork_of": null, "generation": 8}, "gaps": ["asset:data:geo:GSE114007 licence not read", "asset:data:geo:GSE114007 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": ["We used estimateCommonDisp() and estimateTagwiseDisp() function for estimating the dispersion, and exactTest() function for tagwise tests using the exact negative binomial test."], "order_basis": "analysis_only", "id": "assay:1"}]}