Bioinformatics-Based Analysis of the lncRNA-miRNA-mRNA Network and TF Regulatory Network to Explore the Regulation Mechanism in Spinal Cord Ischemia/Reperfusion Injury.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33986769", "kind": "science-record", "revision": 7, "content_hash": "sha256:1d92f2bd058d3358fb57130ecaaad712e97a53b4a8a8c06efb1405375f6086d6", "created_at": "2026-11-01T15:41:35Z", "updated_at": "2026-11-01T22:03:44Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bioinformatics-Based Analysis of the lncRNA-miRNA-mRNA Network and TF Regulatory Network to Explore the Regulation Mechanism in Spinal Cord Ischemia/Reperfusion Injury.", "doi": "10.3389/fgene.2021.650180", "pmid": "33986769", "authors": ["Dan Wang", "Limei Wang", "Jie Han", "Zaili Zhang", "Bo Fang", "Fengshou Chen"], "journal": "Frontiers in genetics", "year": 2021, "abstract": "BACKGROUND: Spinal cord ischemia/reperfusion injury (SCII) is a catastrophic complication involved with cardiovascular, spine, and thoracic surgeries and can lead to paraplegia. Nevertheless, the molecular mechanism of SCII remain ill-defined.\nMETHODS: Expression profiling (GSE138966) data were obtained from GEO database. Then, differentially expressed (DE) lncRNAs and DEmRNAs were screened out with p < 0.05, and | fold change| > 1.5. Aberrant miRNAs expression in SCII was obtained from PubMed. Functional enrichment analysis of overlapping DEmRNAs between predicted mRNAs in miRDB database and DEmRNAs obtained from GSE138966 was performed using cluster Profiler R package. The lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network was established in light of ceRNA theory. The key lncRNAs in the ceRNA network were identified by topological analysis. Subsequently, key lncRNAs related ceRNA-pathway network and transcription factors (TFs)-mRNAs network were constructed. Simultaneously, the expression levels of hub genes were measured via qRT-PCR.\nRESULTS: The results in this study indicated that 76 miRNAs, 1373 lncRNAs, and 4813 mRNAs were differentially expressed in SCII. A SCII-related ceRNA network was constructed with 154 ncRNAs, 139 mRNAs, and 51 miRNAs. According topological analysis, six lncRNAs (NONRATT019236.2, NONRATT009530.2, NONRATT026999.2, TCONS_00032391, NONRATT023112.2, and NONRATT021956.2) were selected to establish the ceRNA-pathway network, and then two candidate hub lncRNAs (NONRATT009530.2 and NONRATT026999.2) were identified. Subsequently, two lncRNA-miRNA-mRNA regulatory axes were identified. NONRATT026999.2 and NONRATT009530.2 might involve SCII via miR-20b-5p/Map3k8 axis based on the complex ceRNA network. SP1 and Hnf4a acting as important TFs might regulate Map3k8. Furthermore, qRT-PCR results showed that the NONRATT009530.2, NONRATT026999.2, Map3k8, Hfn4a, and SP1 were significantly upregulated in SCII of rats, while the miR-20b-5p was downregulated.\nCONCLUSION: Our results offer a new insight to understand the ceRNA regulation mechanism in SCII and identify highlighted lncRNA-miRNA-mRNA axes and two key TFs as potential targets for prevention and treatment of SCII.", "claims": [{"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33986769", "locator": "sections[24] \"Data Availability Statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."}], "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:33986769"], "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:GSE138966"], "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:GSE138966"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33986769", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2021.650180", "sha256": "sha256:37d4cb6ac3d74f48b30bcc771aec0c1494f0af792ac4607de05bb9651bcd6745", "bytes": 55667, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fgene.2021.650180", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8110913", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE138966", "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=GSE138966", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE138966", "version": null, "note": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4125368", "GSM4125369", "GSM4125370", "GSM4125371", "GSM4125372", "GSM4125373"], "sample_count": 6, "group_sizes": null, "group_sizes_basis": null, "platform": "22396", "taxon": "Rattus norvegicus", "title": "Long non-coding RNA and mRNA transcriptomic profiles after ischemia-reperfusion injury in rat spinal cord.", "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:33986769:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:275692923c36a18210409e6ac39861b57593eb9d6d602f56ae4ba57bf8fe3d56", "bytes": 866, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#T1", "version": null, "note": "qRT-PCR primers sequences used in this study.", "structure": {"pmcid": "PMC8110913", "section_index": 11, "section_title": "Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR)", "row_count": 9, "column_count": 3}, "table": {"label": "TABLE 1", "caption": "qRT-PCR primers sequences used in this study.", "rows": [["miRNA/gene", "Forward primer", "Reverse primer"], ["miR-20b-5p", "5′-CAAAGUGCTCATAGTGCAGGTAG-3′", "−"], ["NONRATT009530.2", "5′-GTGCTCTTGTCTGTGTCTGTGTCC-3′", "5′-CACTTCTGAAGCCACTGCCACTC-3′"], ["NONRATT026999.2", "5′-GTGAAGGTGCTTAACGCCAGGAG-3′", "5′-GCCGCAGAACACGCATCCTC-3′"], ["Map3k8", "5′-CGTGAGTAGTGGTGTCTGCCTTG-3′", "5′-GGAATCTGTGTCTGCTGCTGAGTG-3′"], ["SP1", "5′-CTGCAAGGGTCTGATTCTCTA-3′", "5′-AGCTTGTCCACCTTGAACTA-3′"], ["Hnf4a", "5′-TGCCAACCTCAACTCATCCAACAG-3′", "5′-TCCTCACGCTCCTCCTGAAGAATC-3′"], ["GAPDH", "5′-GGGAAACTGTGGCGTGAT-3′", "5′-GGGTGTCGCTGTTGAAGT-3′"], ["U6", "5′-CTCGCTTCGGCAGCACA-3′", "5′-AACGCTTCACGAATTTGCGT-3′"]], "row_count": 9, "column_count": 3, "numeric_cells": 18, "header_rows": 1, "locator": "section[11]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:33986769:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:d07e66580b138f389f5920ddf8118073129b6ede537a8aa64e322f9eb4b8c2bc", "bytes": 1028, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[1]#T2", "version": null, "note": "The basic characteristics of SCII DEmiRNA datasets.", "structure": {"pmcid": "PMC8110913", "section_index": 14, "section_title": "Identification of DEmiRNAs, DElncRNAs, and DEmRNAs", "row_count": 10, "column_count": 6}, "table": {"label": "TABLE 2", "caption": "The basic characteristics of SCII DEmiRNA datasets.", "rows": [["References", "Data set", "species", "Samples", "Assay/sequencing type", "Validated"], ["Hu et al., 2013", "HJR2013", "Rat", "Spinal cord tissues", "microRNA microarrays", "qRT-PCR"], ["Li et al., 2015", "LL2015", "Rat", "Spinal cord tissues", "qRT-PCR", "−"], ["Li J. A. et al., 2016", "LJA2016", "Rat", "Spinal cord tissues", "microarray analysis", "−"], ["Li X. Q. et al., 2016", "LXQ2016", "Rat", "Spinal cord tissues", "microRNA microarrays", "qRT-PCR"], ["Li et al., 2018", "LXQ2018", "Rat", "Spinal cord tissues", "qRT-PCR", "−"], ["Liu et al., 2018", "LY2018", "Rat", "Spinal cord tissues", "RT-PCR", "−"], ["Wang X. et al., 2019", "WXY2019", "Rat", "Spinal cord tissues", "qRT-PCR", "−"], ["Fang et al., 2020", "HF2020", "Rat", "Spinal cord tissues", "qRT-PCR", "−"], ["Liu et al., 2020", "ZGL2020", "Rat", "Spinal cord tissues", "microRNA microarrays", "qRT-PCR"]], "row_count": 10, "column_count": 6, "numeric_cells": 18, "header_rows": 1, "locator": "section[14]/table-wrap[1]#T2"}}, {"id": "asset:table:pmid:33986769:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ec3f6a00fb6c97b5bcb1ffe1775f35f0df42cc0c92db4e96e6c1c0d13e1af0f1", "bytes": 1609, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": 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["rno-miR-30c-5p", "0.19202477", "0.35828877", "28", "Up", "miRNA"], ["TCONS_00032291", "0.13638041", "0.35263158", "19", "Down", "lncRNA"], ["rno-miR-330-5p", "0.0980652", "0.35078534", "19", "Up", "miRNA"], ["rno-miR-672-3p", "0.09227397", "0.3972332", "19", "Up", "miRNA"], ["rno-miR-105", "0.0628762", "0.2942899", "16", "Up", "miRNA"], ["rno-miR-743b-3p", "0.18723038", "0.35608309", "15", "Down", "miRNA"], ["rno-miR-200b-3p", "0.06427476", "0.33059211", "14", "Up", "miRNA"], ["rno-miR-19b-3p", "0.15041392", "0.36144578", "13", "Down", "miRNA"], ["rno-miR-20b-5p", "0.1312424", "0.34883721", "13", "Down", "miRNA"], ["rno-miR-19a-3p", "0.1326247", "0.31007752", "12", "Down", "miRNA"], ["rno-miR-182", "0.12489841", "0.33057851", "12", "Down", "miRNA"], ["NONRATT026999.2", "0.09955192", "0.2942899", "12", "Up", "lncRNA"], ["NONRATT023112.2", "0.05022828", "0.33895447", "12", "Down", "lncRNA"], ["rno-miR-185-3p", "0.04457109", "0.35502959", "12", "Up", "miRNA"], ["rno-miR-149-5p", "0.0367307", "0.32576985", "12", "Up", "miRNA"], ["NONRATT019326.2", "0.21525703", "0.35928144", "11", "Up", "lncRNA"], ["NONRATT009530.2", "0.19168702", "0.36474164", "11", "Up", "lncRNA"], ["Camk1d", "0.07605598", "0.40361446", "11", "Down", "mRNA"], ["rno-miR-98-5p", "0.09080408", "0.2919708", "10", "Down", "miRNA"], ["rno-miR-873-5p", "0.03179831", "0.27762431", "10", "Up", "miRNA"], ["rno-miR-381-3p", "0.09927927", "0.30781011", "9", "Down", "miRNA"], ["NONRATT000711.2", "0.09817817", "0.28103044", "9", "Up", "lncRNA"], ["rno-miR-125b-5p", "0.0752682", "0.34582133", "9", "Down", "miRNA"], ["rno-miR-148a-3p", "0.05789145", "0.30075188", "9", "Down", "miRNA"], ["NONRATT021956.2", "0.05212423", "0.30044843", "9", "Down", "lncRNA"], ["rno-miR-323-3p", "0.03536281", "0.32967033", "9", "Up", "miRNA"], ["TCONS_00019774", "0.03441627", "0.29777778", "9", "Down", "lncRNA"], ["NONRATT023352.2", "0.02355001", "0.29558824", "9", "Down", "lncRNA"], ["rno-miR-204-3p", "0.01989314", "0.35765125", "9", "Up", "miRNA"], ["Slitrk1", "0.01385154", "0.30454545", "9", "Down", "mRNA"], ["NONRATT022294.2", "0.09576549", "0.3", "8", "Up", "lncRNA"], ["Angptl4", "0.09104243", "0.2484472", "8", "Up", "mRNA"], ["NONRATT028502.2", "0.08986369", "0.29411765", "8", "Down", "lncRNA"], ["NONRATT016973.2", "0.08342507", "0.27272727", "8", "Up", "lncRNA"], ["rno-miR-181b-5p", "0.07952858", "0.32608696", "8", "Down", "miRNA"], ["NONRATT030423.2", "0.05755366", "0.32345013", "8", "Up", "lncRNA"], ["Sdc1", "0.03704544", "0.3125", "8", "Up", "mRNA"], ["rno-miR-291a-3p", "0.02976731", "0.28920863", "8", "Down", "miRNA"], ["NONRATT030971.2", "0.02028265", "0.29646018", "8", "Down", "lncRNA"], ["Ggt7", "0.01764119", "0.35387324", "8", "Down", "mRNA"], ["Map3k12", "0.01396893", "0.29955291", "8", "Down", "mRNA"], ["NONRATT012376.2", "0.07174532", "0.32697548", "7", "Down", "lncRNA"], ["NONRATT015872.2", "0.06823347", "0.318542", "7", "Up", "lncRNA"], ["TCONS_00005669", "0.0267793", 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"bytes": 802, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[18]/table-wrap[2]#T5", "version": null, "note": "Basic information of the candidate 6 DElncRNAs.", "structure": {"pmcid": "PMC8110913", "section_index": 18, "section_title": "Topological Analysis of the ceRNA Network", "row_count": 7, "column_count": 7}, "table": {"label": "TABLE 5", "caption": "Basic information of the candidate 6 DElncRNAs.", "rows": [["DE-lncRNAs", "Fold change", "P-value", "Degree", "Betweeness centrality", "Closeness centrality", "Down/Up"], ["NONRATT026999.2", "2.62678022728", "0.018017", "12", "0.099551912", "0.2942899", "Up"], ["NONRATT019326.2", "2.56469830552", "0.034967", "11", "0.21525703", "0.35928144", "Up"], ["NONRATT009530.2", "355.506999015", "0.036493", "11", "0.19168702", "0.36474164", "Up"], ["TCONS_00032291", "−3.07336006", "0.034165", "19", "0.13638041", "0.35263158", "Down"], ["NONRATT023112.2", "−3.29641383", 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"data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "centrality"}}, {"id": "method-3", "family": null, "specific": null, "label": "Two-class differential analysis using Student’s t-test", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "reordered", "quote": "“Two-class differential analysis was applied to explore DEmRNAs and DElncRNAs between SCII and sham rats.” “R package (Robinson et al., 2010), a public available statistical computing software, was used to performed Student’s t-test (Mak et al., 2020).” “The mRNA and lncRNA expression profiles were obtained from dataset GSE138966 (3 pairs of rat post 48 h of SCII and sham tissues).”"}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": 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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": ["GSE138966"], "resolved_accessions": ["GSE138966"], "statements": ["The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."], "basis": "The paper names GSE138966 in GEO database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["pathway_enrich"], "assets": ["source:pmid:33986769", "data:geo:GSE138966", "asset:table:pmid:33986769:1", "asset:table:pmid:33986769:2", "asset:table:pmid:33986769:3", "asset:table:pmid:33986769:4", "asset:table:pmid:33986769:5"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE138966"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:30:02Z", "independence": "single_reader"}, "evidence_check": {"method": "reordered", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 47451, "completion_tokens": 1246, "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:33986769", "type": "paper", "label": "pmid:33986769"}, {"id": "source:pmid:33986769", "type": "manuscript", "label": "PMID 33986769 full text"}, {"id": "data:geo:GSE138966", "type": "dataset", "label": "GEO GSE138966"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33986769", "type": "paper", "label": "pmid:33986769"}, {"id": "source:pmid:33986769", "type": "manuscript", "label": "PMID 33986769 full text"}, {"id": "data:geo:GSE138966", "type": "dataset", "label": "GEO GSE138966"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33986769", "type": "extraction", "used": ["source:pmid:33986769"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE138966", "type": "accession_resolution", "used": ["data:geo:GSE138966"], "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:33986769", "parent_hash": "sha256:fe03d72c394d13fae43a35d6882923c4fc27be09a2d49167b52c51138875deb0", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE138966 licence not read", "asset:data:geo:GSE138966 not downloaded", "execution.not_run", "method.reader_named_unmapped", "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": 0.642, "evidence": ["P1 were significantly upregulated in SCII of rats, while the miR-20b-5p was downregulated. 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