Identification and Functional Characterization of Long Non-coding RNA MIR22HG as a Tumor Suppressor for Hepatocellular Carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30083257", "kind": "science-record", "revision": 8, "content_hash": "sha256:ab612174dd1ba13bb3c9ac3299df55eedec99a0ab3431fb73f971c910862d038", "created_at": "2026-11-01T15:40:36Z", "updated_at": "2026-11-01T21:59:58Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and Functional Characterization of Long Non-coding RNA MIR22HG as a Tumor Suppressor for Hepatocellular Carcinoma.", "doi": "10.7150/thno.22493", "pmid": "30083257", "authors": ["Dong-Yan Zhang", "Xue-Jing Zou", "Chuan-Hui Cao", "Ting Zhang", "Ling Lei", "Xiao-Long Qi", "Li Liu", "De-Hua Wu"], "journal": "Theranostics", "year": 2018, "abstract": "Long non-coding RNAs (lncRNAs) have recently been identified as critical regulators in tumor initiation and development. However, the function of lncRNAs in human hepatocellular carcinoma (HCC) remains largely unknown. Our study was designed to explore the biological function and clinical implication of lncRNA MIR22HG in HCC. Methods: We evaluated MIR22HG expression in 52-patient, 145-patient, TCGA, and GSE14520 HCC cohorts. The effects of MIR22HG on HCC were analyzed in terms of proliferation, invasion, and metastasis, both in vitro and in vivo. The mechanism of MIR22HG action was explored through bioinformatics, luciferase reporter, and RNA immunoprecipitation analyses. Results:MIR22HG expression was significantly down-regulated in 4 independent HCC cohorts compared to that in controls. Its low expression was associated with tumor progression and poor prognosis of patients with HCC. Forced expression of MIR22HG in HCC cells significantly suppressed proliferation, invasion, and metastasis in vitro and in vivo. Mechanistically, MIR22HG derived miR-22-3p to target high mobility group box 1 (HMGB1), thereby inactivating HMGB1 downstream pathways. Additionally, MIR22HG directly interacted with HuR and regulated its subcellular localization. MIR22HG competitively bound to human antigen R (HuR), resulting in weakened expression of HuR-stabilized oncogenes, such as β-catenin. Furthermore, miR-22-3p suppression, HuR or HMGB1 overexpression rescued the inhibitory effects caused by MIR22HG overexpression. Conclusion: Our findings revealed that MIR22HG plays a key role in tumor progression by suppressing the proliferation, invasion, and metastasis of tumor cells, suggesting its potential role as a tumor suppressor and prognostic biomarker in HCC.", "claims": [{"id": "claim-method", "statement": "The t-test or one-way analysis of variance (ANOVA) for comparison of two groups, multi-way classification ANOVA for cell proliferation, Pearson's correlation for analyzing the correlation between miR-22-3p and MIR22HG or HMGB1, Kaplan-Meier for survival analysis, and univariate and multivariate Cox regression for determining the independent factors of survival were used in this study. “TCGA cohort”: A cohort from the TCGA (https://tcga-data.nci.nih.gov/tcga/) database including 327 HCC patients with MIR22HG or miR-22-3-expression data, as well as follow-up information, were included in our study to explore the expression levels of MIR22HG or miR-22-3p in HCC. “GSE14520 and 10694 cohorts”: Two sets of microarray data (GEO accession numbers GSE14520 40 and GSE10694 41) were downloaded from the GEO (http://www.ncbi.nlm.nih.gov/geo/) to validate MIR22HG- or miR-22-3p-expression level in HCC.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30083257", "locator": "sections[17] \"Statistical Analysis\" paragraph 2", "quote": "The t-test or one-way analysis of variance (ANOVA) for comparison of two groups, multi-way classification ANOVA for cell proliferation, Pearson's correlation for analyzing the correlation between miR-22-3p and MIR22HG or HMGB1, Kaplan-Meier for survival analysis, and univariate and multivariate Cox regression for determining the independent factors of survival were used in this study."}, {"asset": "source:pmid:30083257", "locator": "sections[14] \"Gene-expression Datasets\" paragraph 2", "quote": "“TCGA cohort”: A cohort from the TCGA (https://tcga-data.nci.nih.gov/tcga/) database including 327 HCC patients with MIR22HG or miR-22-3-expression data, as well as follow-up information, were included in our study to explore the expression levels of MIR22HG or miR-22-3p in HCC."}, {"asset": "source:pmid:30083257", "locator": "sections[14] \"Gene-expression Datasets\" paragraph 3", "quote": "“GSE14520 and 10694 cohorts”: Two sets of microarray data (GEO accession numbers GSE14520 40 and GSE10694 41) were downloaded from the GEO (http://www.ncbi.nlm.nih.gov/geo/) to validate MIR22HG- or miR-22-3p-expression level in HCC."}], "state": "complete"}, {"id": "claim-data-access", "statement": "“TCGA cohort”: A cohort from the TCGA (https://tcga-data.nci.nih.gov/tcga/) database including 327 HCC patients with MIR22HG or miR-22-3-expression data, as well as follow-up information, were included in our study to explore the expression levels of MIR22HG or miR-22-3p in HCC. The genome-wide expression profiles, including 377 samples, were downloaded from the TCGA dataset.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30083257", "locator": "sections[14] \"Gene-expression Datasets\" paragraph 2", "quote": "“TCGA cohort”: A cohort from the TCGA (https://tcga-data.nci.nih.gov/tcga/) database including 327 HCC patients with MIR22HG or miR-22-3-expression data, as well as follow-up information, were included in our study to explore the expression levels of MIR22HG or miR-22-3p in HCC."}, {"asset": "source:pmid:30083257", "locator": "sections[15] \"GSEA\" paragraph 2", "quote": "The genome-wide expression profiles, including 377 samples, were downloaded from the TCGA dataset."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using univariate and multivariate Cox regression analysis in the 145-patient HCC cohort, low MIR22HG expression was found to be an independent prognostic factor for overall survival (95% CI: 0.270–0.912; P = 0.024).", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "Furthermore, univariate Cox regression analysis revealed that the mortality risk of patients with HCC was significantly associated with low MIR22HG expression (95% CI: 0.227-0.735; P = 0.003), PVTT (95% CI: 2.008-6.578; P< 0.001), clinical stage (95% CI: 1.077-3.101; P = 0.025), tumor relapse (95% CI: 1.164-3.249; P = 0.011), and tumor size (95% CI: 1.123-3.308; P = 0.017) (Table 1)."}, "evidence": [{"asset": "source:pmid:30083257", "locator": "sections[4] \"Low Expression of MIR22HG Correlates with Tumor Progression and Poor Prognosis in Human HCC\" paragraph 3", "quote": "Survival analysis of the 145-patient cohort showed that patients with HCC and high MIR22HG expression exhibited better overall survival (OS; P = 0.001) and disease-free survival (DFS; P = 0.042) as compared with those with low MIR22HG expression (Figure 1F)."}, {"asset": "source:pmid:30083257", "locator": "sections[4] \"Low Expression of MIR22HG Correlates with Tumor Progression and Poor Prognosis in Human HCC\" paragraph 3", "quote": "Furthermore, univariate Cox regression analysis revealed that the mortality risk of patients with HCC was significantly associated with low MIR22HG expression (95% CI: 0.227-0.735; P = 0.003), PVTT (95% CI: 2.008-6.578; P< 0.001), clinical stage (95% CI: 1.077-3.101; P = 0.025), tumor relapse (95% CI: 1.164-3.249; P = 0.011), and tumor size (95% CI: 1.123-3.308; P = 0.017) (Table 1)."}, {"asset": "source:pmid:30083257", "locator": "sections[4] \"Low Expression of MIR22HG Correlates with Tumor Progression and Poor Prognosis in Human HCC\" paragraph 3", "quote": "In multivariate analysis, lower MIR22HG expression emerged as an independent prognostic factor for OS in patients with HCC (95% CI: 0.270-0.912; P = 0.024; Table 1)."}, {"asset": "source:pmid:30083257", "locator": "sections[4] \"Low Expression of MIR22HG Correlates with Tumor Progression and Poor Prognosis in Human HCC\" paragraph 4", "quote": "Univariate and multivariate analyses of OS in the 145-patient cohort by Cox regression analysis."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using univariate and multivariate Cox regression analysis in the 145-patient HCC cohort, low MIR22HG expression was found to be an independent prognostic factor for overall survival (95% CI: 0.270–0.912; P = 0.024).", "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:30083257"], "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:GSE10694"], "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:GSE10694"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:30083257", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7150/thno.22493", "sha256": "sha256:e0355e8f9fcd4537c7db5191e338d970599a76950a3a07a8fefd7c24ede30988", "bytes": 51417, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.7150/thno.22493", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6071531", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE10694", "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=GSE10694", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE10694", "version": null, "note": "“TCGA cohort”: A cohort from the TCGA (https://tcga-data.nci.nih.gov/tcga/) database including 327 HCC patients with MIR22HG or miR-22-3-expression data, as well as follow-up information, were included in our study to explore the expression levels of MIR22HG or miR-22-3p in HCC. The genome-wide expression profiles, including 377 samples, were downloaded from the TCGA dataset.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "“TCGA cohort”: A cohort from the TCGA (https://tcga-data.nci.nih.gov/tcga/) database including 327 HCC patients with MIR22HG or miR-22-3-expression data, as well as follow-up information, were included in our study to explore the expression levels of MIR22HG or miR-22-3p in HCC. The genome-wide expression profiles, including 377 samples, were downloaded from the TCGA dataset.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM270322", "GSM270323", "GSM270324", "GSM270325", "GSM270326", "GSM270327", "GSM270328", "GSM270329", "GSM270330", "GSM270331", "GSM270332", "GSM270333", "GSM270334", "GSM270335", "GSM270336", "GSM270337", "GSM270338", "GSM270339", "GSM270340", "GSM270341", "GSM270342", "GSM270343", "GSM270344", "GSM270345", "GSM270346", "GSM270347", "GSM270348", "GSM270349", "GSM270350", "GSM270351", "GSM270352", "GSM270353", "GSM270354", "GSM270355", "GSM270356", "GSM270357", "GSM270358", "GSM270359", "GSM270360", "GSM270361", "GSM270362", "GSM270363", "GSM270364", "GSM270365", "GSM270366", "GSM270367", "GSM270368", "GSM270369", "GSM270370", "GSM270371", "GSM270372", "GSM270373", "GSM270374", "GSM270375", "GSM270376", "GSM270377", "GSM270378", "GSM270379", "GSM270380", "GSM270381", "GSM270382", "GSM270383", "GSM270384", "GSM270385", "GSM270386", "GSM270387", "GSM270388", "GSM270389", "GSM270390", "GSM270391", "GSM270392", "GSM270393", "GSM270394", "GSM270395", "GSM270396", "GSM270397", "GSM270398", "GSM270399", "GSM270400", "GSM270401", "GSM270402", "GSM270403", "GSM270404", "GSM270405", "GSM270406", "GSM270407", "GSM270408", "GSM270409", "GSM270410", "GSM270411", "GSM270412", "GSM270413", "GSM270414", "GSM270415", "GSM270416", "GSM270417", "GSM270418", "GSM270419", "GSM270420", "GSM270421", "GSM270422", "GSM270423", "GSM270424", "GSM270425", "GSM270426", "GSM270427", "GSM270428", "GSM270429", "GSM270430", "GSM270431", "GSM270432", "GSM270433", "GSM270434", "GSM270435", "GSM270436", "GSM270437", "GSM270438", "GSM270439", "GSM270440", "GSM270441", "GSM270442", "GSM270443", "GSM270444", "GSM270445", "GSM270446", "GSM270447", "GSM270448", "GSM270449", "GSM270450", "GSM270451", "GSM270452", "GSM270453", "GSM270454", "GSM270455", "GSM270456", "GSM270457", "GSM270458", "GSM270459", "GSM270460", "GSM270461", "GSM270462", "GSM270463", "GSM270464", "GSM270465", "GSM270466", "GSM270467", "GSM270468", "GSM270469", "GSM270470", "GSM270471", "GSM270472", "GSM270473", "GSM270474", "GSM270475", "GSM270476", "GSM270477", "GSM270478", "GSM270479", "GSM270480", "GSM270481", "GSM270482", "GSM270483", "GSM270484", "GSM270485", "GSM270486", "GSM270487"], "sample_count": 166, "group_sizes": null, "group_sizes_basis": null, "platform": "6542", "taxon": "Homo sapiens", "title": "MicroRNAs expression profile in human hepatocellular carcinoma", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE14520", "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=GSE14520", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE14520", "version": null, "note": "“TCGA cohort”: A cohort from the TCGA (https://tcga-data.nci.nih.gov/tcga/) database including 327 HCC patients with MIR22HG or miR-22-3-expression data, as well as follow-up information, were included in our study to explore the expression levels of MIR22HG or miR-22-3p in HCC. The genome-wide expression profiles, including 377 samples, were downloaded from the TCGA dataset.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "“TCGA cohort”: A cohort from the TCGA (https://tcga-data.nci.nih.gov/tcga/) database including 327 HCC patients with MIR22HG or miR-22-3-expression data, as well as follow-up information, were included in our study to explore the expression levels of MIR22HG or miR-22-3p in HCC. The genome-wide expression profiles, including 377 samples, were downloaded from the TCGA dataset.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM362947", "GSM362948", "GSM362949", "GSM362950", "GSM362951", "GSM362952", "GSM362953", "GSM362954", "GSM362955", "GSM362956", "GSM362957", "GSM362958", "GSM362959", "GSM362960", "GSM362961", "GSM362962", "GSM362963", "GSM362964", "GSM362965", "GSM362966", "GSM362967", "GSM362968", "GSM362969", "GSM362970", "GSM362971", "GSM362972", "GSM362973", "GSM362974", "GSM362975", "GSM362976", "GSM362977", "GSM362978", "GSM362979", "GSM362980", "GSM362981", "GSM362982", "GSM362983", "GSM362984", "GSM362985", "GSM362986", "GSM362987", "GSM362988", "GSM362989", "GSM362990", "GSM362991", "GSM362992", "GSM362993", "GSM362994", "GSM362995", "GSM362996", "GSM362997", "GSM362998", "GSM362999", "GSM363000", "GSM363001", "GSM363002", "GSM363003", "GSM363004", "GSM363005", "GSM363006", "GSM363007", "GSM363008", "GSM363009", "GSM363010", "GSM363011", "GSM363012", "GSM363013", "GSM363014", "GSM363015", "GSM363016", "GSM363017", "GSM363018", "GSM363019", "GSM363020", "GSM363021", "GSM363022", "GSM363023", "GSM363024", "GSM363025", "GSM363026", "GSM363027", "GSM363028", "GSM363029", "GSM363030", "GSM363031", "GSM363032", "GSM363033", "GSM363034", "GSM363035", "GSM363036", "GSM363037", "GSM363038", "GSM363039", "GSM363040", "GSM363041", "GSM363042", "GSM363043", "GSM363044", "GSM363045", "GSM363046", "GSM363047", "GSM363048", "GSM363049", "GSM363050", "GSM363051", "GSM363052", "GSM363053", "GSM363054", "GSM363055", "GSM363056", "GSM363057", "GSM363058", "GSM363059", "GSM363060", "GSM363061", "GSM363062", "GSM363063", "GSM363064", "GSM363065", "GSM363066", "GSM363067", "GSM363068", "GSM363069", "GSM363070", "GSM363071", "GSM363072", "GSM363073", "GSM363074", "GSM363075", "GSM363076", "GSM363077", "GSM363078", "GSM363079", "GSM363080", "GSM363081", "GSM363082", "GSM363083", "GSM363084", "GSM363085", "GSM363086", "GSM363087", "GSM363088", "GSM363089", "GSM363090", "GSM363091", "GSM363092", "GSM363093", "GSM363094", "GSM363095", "GSM363096", "GSM363097", "GSM363098", "GSM363099", "GSM363100", "GSM363101", "GSM363102", "GSM363103", "GSM363104", "GSM363105", "GSM363106", "GSM363107", "GSM363108", "GSM363109", "GSM363110", "GSM363111", "GSM363112", "GSM363113", "GSM363114", "GSM363115", "GSM363116", "GSM363117", "GSM363118", "GSM363119", "GSM363120", "GSM363121", "GSM363122", "GSM363123", "GSM363124", "GSM363125", "GSM363126", "GSM363127", "GSM363128", "GSM363129", "GSM363130", "GSM363131", "GSM363132", "GSM363133", "GSM363134", "GSM363135", "GSM363136", "GSM363137", "GSM363138", "GSM363139", "GSM363140", "GSM363141", "GSM363142", "GSM363143", "GSM363144", "GSM363145", "GSM363146", "GSM363147", "GSM363148", "GSM363149", "GSM363150", "GSM363151", "GSM363152", "GSM363153", "GSM363154", "GSM363155", "GSM363156", "GSM363157", "GSM363158", "GSM363159", "GSM363160", "GSM363161", "GSM363162", "GSM363163", "GSM363164", "GSM363165", "GSM363166", "GSM363167", "GSM363168", "GSM363169", "GSM363170", "GSM363171", "GSM363172", "GSM363173", "GSM363174", "GSM363175", "GSM363176", "GSM363177", "GSM363178", "GSM363179", "GSM363180", "GSM363181", "GSM363182", "GSM363183", "GSM363184", "GSM363185", "GSM363186", "GSM363187", "GSM363188", "GSM363189", "GSM363190", "GSM363191", "GSM363192", "GSM363193", "GSM363194", "GSM363195", "GSM363196", "GSM363197", "GSM363198", "GSM363199", "GSM363200", "GSM363201", "GSM363202", "GSM363203", "GSM363204", "GSM363205", "GSM363206", "GSM363207", "GSM363208", "GSM363209", "GSM363210", "GSM363211", "GSM363212", "GSM363213", "GSM363214", "GSM363215", "GSM363216", "GSM363217", "GSM363218", "GSM363219", "GSM363220", "GSM363221", "GSM363222", "GSM363223", "GSM363224", "GSM363225", "GSM363226", "GSM363227", "GSM363228", "GSM363229", "GSM363230", "GSM363231", "GSM363232", "GSM363233", "GSM363234", "GSM363235", "GSM363236", "GSM363237", "GSM363238", "GSM363239", "GSM363240", "GSM363241", "GSM363242", "GSM363243", "GSM363244", "GSM363245", "GSM363246", "GSM363247", "GSM363248", "GSM363249", "GSM363250", "GSM363251", "GSM363252", "GSM363253", "GSM363254", "GSM363255", "GSM363256", "GSM363257", "GSM363258", "GSM363259", "GSM363260", "GSM363261", "GSM363262", "GSM363263", "GSM363264", "GSM363265", "GSM363266", "GSM363267", "GSM363268", "GSM363269", "GSM363270", "GSM363271", "GSM363272", "GSM363273", "GSM363274", "GSM363275", "GSM363276", "GSM363277", "GSM363278", "GSM363279", "GSM363280", "GSM363281", "GSM363282", "GSM363283", "GSM363284", "GSM363285", "GSM363286", "GSM363287", "GSM363288", "GSM363289", "GSM363290", "GSM363291", "GSM363292", "GSM363293", "GSM363294", "GSM363295", "GSM363296", "GSM363297", "GSM363298", "GSM363299", "GSM363300", "GSM363301", "GSM363302", "GSM363303", "GSM363304", "GSM363305", "GSM363306", "GSM363307", "GSM363308", "GSM363309", "GSM363310", "GSM363311", "GSM363312", "GSM363313", "GSM363314", "GSM363315", "GSM363316", "GSM363317", "GSM363318", "GSM363319", "GSM363320", "GSM363321", "GSM363322", "GSM363323", "GSM363324", "GSM363325", "GSM363326", "GSM363327", "GSM363328", "GSM363329", "GSM363330", "GSM363331", "GSM363332", "GSM363333", "GSM363334", "GSM363335", "GSM363336", "GSM363337", "GSM363338", "GSM363339", "GSM363340", "GSM363341", "GSM363342", "GSM363343", "GSM363344", "GSM363345", "GSM363346", "GSM363347", "GSM363348", "GSM363349", "GSM363350", "GSM363351", "GSM363352", "GSM363353", "GSM363354", "GSM363355", "GSM363356", "GSM363357", "GSM363358", "GSM363359", "GSM363360", "GSM363361", "GSM363362", "GSM363363", "GSM363364", "GSM363365", "GSM363366", "GSM363367", "GSM363368", "GSM363369", "GSM363370", "GSM363371", "GSM363372", "GSM363373", "GSM363374", "GSM363375", "GSM363376", "GSM363378", "GSM363380", "GSM363381", "GSM363382", "GSM363384", "GSM363386", "GSM363388", "GSM363391", "GSM363393", "GSM363397", "GSM363400", "GSM363402", "GSM363404", "GSM363407", "GSM363417", "GSM363420", "GSM363421", "GSM363422", "GSM363423", "GSM363424", "GSM363425", "GSM363426", "GSM363427", "GSM363428", "GSM363429", "GSM363430", "GSM363431", "GSM363432", "GSM363433", "GSM363434", "GSM363435", "GSM363436", "GSM363437", "GSM363438", "GSM363439", "GSM363440", "GSM363441", "GSM363442", "GSM363443", "GSM363444", "GSM363445", "GSM363446", "GSM363447", "GSM363448", "GSM363449", "GSM363450", "GSM363451", "GSM712532", "GSM712533", "GSM712534", "GSM712535", "GSM712536", "GSM712537", "GSM712538", "GSM712539", "GSM712540", "GSM712541", "GSM712542"], "sample_count": 488, "group_sizes": null, "group_sizes_basis": null, "platform": "3921;571", "taxon": "Homo sapiens", "title": "Gene expression data of human hepatocellular carcinoma (HCC)", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE28865", "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=GSE28865", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE28865", "version": null, "note": "“TCGA cohort”: A cohort from the TCGA (https://tcga-data.nci.nih.gov/tcga/) database including 327 HCC patients with MIR22HG or miR-22-3-expression data, as well as follow-up information, were included in our study to explore the expression levels of MIR22HG or miR-22-3p in HCC. The genome-wide expression profiles, including 377 samples, were downloaded from the TCGA dataset.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "“TCGA cohort”: A cohort from the TCGA (https://tcga-data.nci.nih.gov/tcga/) database including 327 HCC patients with MIR22HG or miR-22-3-expression data, as well as follow-up information, were included in our study to explore the expression levels of MIR22HG or miR-22-3p in HCC. The genome-wide expression profiles, including 377 samples, were downloaded from the TCGA dataset.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM714635", "GSM714636", "GSM714637", "GSM714638", "GSM714639", "GSM714640", "GSM714641", "GSM714642", "GSM714643", "GSM714644", "GSM714645", "GSM714646", "GSM714647", "GSM714678", "GSM714679", "GSM714680", "GSM714681", "GSM714682", "GSM714683", "GSM714684", "GSM714685", "GSM714686", "GSM714687"], "sample_count": 23, "group_sizes": null, "group_sizes_basis": null, "platform": "10999", "taxon": "Homo sapiens", "title": "A quantitative analysis of CLIP methods for identifying binding sites of RNA-binding proteins", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE58043", "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=GSE58043", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE58043", "version": null, "note": "“TCGA cohort”: A cohort from the TCGA (https://tcga-data.nci.nih.gov/tcga/) database including 327 HCC patients with MIR22HG or miR-22-3-expression data, as well as follow-up information, were included in our study to explore the expression levels of MIR22HG or miR-22-3p in HCC. The genome-wide expression profiles, including 377 samples, were downloaded from the TCGA dataset.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "“TCGA cohort”: A cohort from the TCGA (https://tcga-data.nci.nih.gov/tcga/) database including 327 HCC patients with MIR22HG or miR-22-3-expression data, as well as follow-up information, were included in our study to explore the expression levels of MIR22HG or miR-22-3p in HCC. The genome-wide expression profiles, including 377 samples, were downloaded from the TCGA dataset.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM1399798", "GSM1399799", "GSM1399800", "GSM1399801", "GSM1399802", "GSM1399803", "GSM1399804", "GSM1399805", "GSM1399806", "GSM1399807", "GSM1399808", "GSM1399809", "GSM1399810", "GSM1399811"], "sample_count": 14, "group_sizes": null, "group_sizes_basis": null, "platform": "13825", "taxon": "Homo sapiens", "title": "liver cancer tissues: tumor tissues vs. non-tumor tissues", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE6762", "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=GSE6762", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE6762", "version": null, "note": "“TCGA cohort”: A cohort from the TCGA (https://tcga-data.nci.nih.gov/tcga/) database including 327 HCC patients with MIR22HG or miR-22-3-expression data, as well as follow-up information, were included in our study to explore the expression levels of MIR22HG or miR-22-3p in HCC. The genome-wide expression profiles, including 377 samples, were downloaded from the TCGA dataset.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "“TCGA cohort”: A cohort from the TCGA (https://tcga-data.nci.nih.gov/tcga/) database including 327 HCC patients with MIR22HG or miR-22-3-expression data, as well as follow-up information, were included in our study to explore the expression levels of MIR22HG or miR-22-3p in HCC. The genome-wide expression profiles, including 377 samples, were downloaded from the TCGA dataset.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM155829", "GSM155830", "GSM155831", "GSM155832"], "sample_count": 4, "group_sizes": null, "group_sizes_basis": null, "platform": "4693", "taxon": "Homo sapiens", "title": "Replicative Senescence in Primary Fibroblasts", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:30083257:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:2d7dc6878738ccf3c2651d4d48354d3bdb1e0bd5172cdf2945f11a488a63e758", "bytes": 1044, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[4]/table-wrap[1]#T1", "version": null, "note": "Univariate and multivariate analyses of OS in the 145-patient cohort by Cox regression analysis.", "structure": {"pmcid": "PMC6071531", "section_index": 4, "section_title": "Low Expression of MIR22HG Correlates with Tumor Progression and Poor Prognosis in Human HCC", "row_count": 13, "column_count": 8}, "table": {"label": "Table 1", "caption": "Univariate and multivariate analyses of OS in the 145-patient cohort by Cox regression analysis.", "rows": [["Variables", "Univariate analysis", "", "Multivariate analysis"], ["HR", "CI (95%)", "P value", "HR", "CI (95%)", "P value"], ["Gender", "1.232", "0.653-2.324", "0.519", "", "", "", ""], ["Age (years)", "1.092", "0.653-1.827", "0.736", "", "", "", ""], ["Edmondson Grade", "1.234", "0.655-2.327", "0.515", "", "", "", ""], ["Metastasis (distant)", "1.922", "0.696-5.308", "0.208", "", "", "", ""], ["Liver cirrhosis", "0.854", "0.481-1.517", "0.591", "", "", "", ""], ["Tumor number", "1.215", "0.656-2.250", "0.535", "", "", "", ""], ["Portal vein tumor thrombus", "3.634", "2.008-6.578", "0.000*", "", "", "", ""], ["BCLC stage", "1.827", "1.077-3.101", "0.025*", "", "", "", ""], ["Relapse", "1.945", "1.164-3.249", "0.011*", "", "", "", ""], ["Tumor size", "1.928", "1.123-3.308", "0.017*", "", "", "", ""], ["MIR22HG", "0.409", "0.227-0.735", "0.003*", "", "0.496", "0.270-0.912", "0.024*"]], "row_count": 13, "column_count": 8, "numeric_cells": 39, "header_rows": 2, "locator": "section[4]/table-wrap[1]#T1"}}], "gaps": ["asset:data:geo:GSE10694 not downloaded", "asset:data:geo:GSE10694 licence not read", "asset:data:geo:GSE14520 not downloaded", "asset:data:geo:GSE14520 licence not read", "asset:data:geo:GSE28865 not downloaded", "asset:data:geo:GSE28865 licence not read", "asset:data:geo:GSE58043 not downloaded", "asset:data:geo:GSE58043 licence not read", "asset:data:geo:GSE6762 not downloaded", "asset:data:geo:GSE6762 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "reordered", "quote": "The t-test or one-way analysis of variance (ANOVA) for comparison of two groups, multi-way classification ANOVA for cell proliferation, Pearson's correlation for analyzing the correlation between miR-22-3p and MIR22HG or HMGB1, Kaplan-Meier for survival analysis, and univariate and multivariate Cox regression for determining the independent factors of survival were used in this study. “TCGA cohort”: A cohort from the TCGA (https://tcga-data.nci.nih.gov/tcga/) database including 327 HCC patients with MIR22HG or miR-22-3-expression data, as well as follow-up information, were included in our study to explore the expression levels of MIR22HG or miR-22-3p in HCC. “GSE14520 and 10694 cohorts”: Two sets of microarray data (GEO accession numbers GSE14520 40 and GSE10694 41) were downloaded from the GEO (http://www.ncbi.nlm.nih.gov/geo/) to validate MIR22HG- or miR-22-3p-expression level in HCC."}}, {"id": "method-2", "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": 0.8, "band": "high", "quote": "analysis of variance"}}, {"id": "method-3", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "Kaplan-Meier"}}, {"id": "method-4", "family": "correlation_analysis", "specific": "pearson", "label": "Correlation analysis", "dsl_operations": ["pearson_r"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Pearson's correlation"}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "bootstrap_mean_difference", "expected_value": 95.0, "unit": "per cent", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none."}], "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": ["cox_ph"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards."}, "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": ["GSE14520", "GSE10694", "GSE58043", "GSE6762", "GSE28865"], "resolved_accessions": ["GSE14520", "GSE10694", "GSE58043", "GSE6762", "GSE28865"], "statements": ["“TCGA cohort”: A cohort from the TCGA (https://tcga-data.nci.nih.gov/tcga/) database including 327 HCC patients with MIR22HG or miR-22-3-expression data, as well as follow-up information, were included in our study to explore the expression levels of MIR22HG or miR-22-3p in HCC. The genome-wide expression profiles, including 377 samples, were downloaded from the TCGA dataset."], "basis": "The paper names GSE14520, GSE10694, GSE58043, GSE6762, GSE28865 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": ["cox_ph"], "assets": ["source:pmid:30083257", "data:geo:GSE10694", "asset:table:pmid:30083257:1"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE10694"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:35:20Z", "independence": "same_provider"}, "evidence_check": {"method": "reordered", "availability": null}, "calls": 8, "usage": {"prompt_tokens": 115232, "completion_tokens": 7001, "cached_tokens": 2104}}, "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:30083257", "type": "paper", "label": "pmid:30083257"}, {"id": "source:pmid:30083257", "type": "manuscript", "label": "PMID 30083257 full text"}, {"id": "data:geo:GSE10694", "type": "dataset", "label": "GEO GSE10694"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:30083257", "type": "paper", "label": "pmid:30083257"}, {"id": "source:pmid:30083257", "type": "manuscript", "label": "PMID 30083257 full text"}, {"id": "data:geo:GSE10694", "type": "dataset", "label": "GEO GSE10694"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-30083257", "type": "extraction", "used": ["source:pmid:30083257"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE10694", "type": "accession_resolution", "used": ["data:geo:GSE10694"], "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:30083257", "parent_hash": "sha256:b9daffdb0d32483e64d560c66daa674d8f8d981de73abfa67441fcc3362fdc6d", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE10694 licence not read", "asset:data:geo:GSE10694 not downloaded", "asset:data:geo:GSE14520 licence not read", "asset:data:geo:GSE14520 not downloaded", "asset:data:geo:GSE28865 licence not read", "asset:data:geo:GSE28865 not downloaded", "asset:data:geo:GSE58043 licence not read", "asset:data:geo:GSE58043 not downloaded", "asset:data:geo:GSE6762 licence not read", "asset:data:geo:GSE6762 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "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": ["invasion, and metastasis, both in vitro and in vivo. The mechanism of MIR22HG action was explore", "ation, invasion, and metastasis in vitro and in vivo. Mechanistically, MIR22HG derived miR-22-3p", "ife Sciences, Hopkinton, MA, USA) before the mice were sacrificed. Tumors were weighed after removal, and tumo", "intensity in the lungs was examined and the mice were sacrificed. The lung tissues were embedded in paraffin"], "order_basis": "paper_text_order:630", "id": "assay:1"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["the mice. Prior to injection, the cells were transfected with pCMV-luciferase (Genechem Company Ltd.,", "il veins. Prior to injection, the cells were transfected with pCMV-luciferase. After 6 (SK-Hep-1 cell"], "order_basis": "paper_text_order:3787", "id": "assay:2"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["paraffin for hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining. An extra-hepatic metastasis", "lin and eosin (H&E) and immunohistochemical (IHC) staining. An extra-hepatic metastasis model", "issues were embedded in paraffin for H&E and IHC staining. Statistical Analysis Data are pres"], "order_basis": "paper_text_order:4154", "id": "assay:3"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The t-test or one-way analysis of variance (ANOVA) for comparison of two groups, multi-way classification ANOVA for cell proliferation, Pearson's correlation for analyzing the correlation between miR-22-3p and MIR22HG or HMGB1, Kaplan-Meier for survival analysis, and univariate and multivariate Cox regression for determining the independent factors of survival were used in this study. “TCGA cohort”: A cohort from the TCGA (https://tcga-data.nci.nih.gov/tcga/) database including 327 HCC patients with MIR22HG or miR-22-3-expression data, as well as follow-up information, were included in our study to explore the expression levels of MIR22HG or miR-22-3p in HCC. “GSE14520 and 10694 cohorts”: Two sets of microarray data (GEO accession numbers GSE14520 40 and GSE10694 41) were downloaded from the GEO (http://www.ncbi.nlm.nih.gov/geo/) to validate MIR22HG- or miR-22-3p-expression level in HCC."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}