{"data":{"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. 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Resolving one blocker can leave another at the same tier."],"engine":"corpus_engine","engine_provider":"rule_based_v1+lex99e1195c7d6f","run_id":"run-20261023T122449232913","source":"esearch","source_detail":"PubMed mirror biomed_pubmed (read-only)","run_status":"complete","imported_at":"2026-11-03T20:16:52+00:00","generated_at":"2026-11-04T02:47:03+00:00","total_papers":5529,"total_assays_tracked":29,"automatable_assay_families":6,"validated":true,"caveat_count":9,"blocking_caveats":5,"caveats":[{"code":"low_evidence_dominates","basis":["4,152 of 5,529 classifications (75.1%) matched no cue evidence and sit at the 0.05 floor.","34 of 230 data_only calls (14.8%) are in that group."],"claim":"Work type and confidence bands","gloss":"Most records were classified from their title and framing alone, with assay-cue coverage at zero.","detail":"Most classifications in this run rest on no matched evidence at all. At the evidence floor the work type comes from title framing and a fixed prior, not from anything in the paper, so the published work-type split should be read as a rough triage signal rather than a measured distribution. The impact is bounded but not removed: since 2026-10-23 the engine excludes floor-confidence records from the shortlist entirely and publishes them separately as held out, so the recommendation is unaffected even though the census is.","status":"unverified","severity":"high"},{"code":"runtime_is_modelled","basis":["Runtime is summed from published per-assay hour figures. Timing awaits the first executed replication.","4,407 of 5,529 records (79.7%) model to 0.00 hours because no assay was matched, which the ranking then reads as \"cheapest\".","0 of 10 shortlisted records carry a 0.00-hour estimate."],"claim":"Estimated replication runtime","gloss":"The hour figures are estimates built from assay mentions; timing awaits the first executed replication.","detail":"The hour figures are a cost model derived from the bench steps implied by each matched assay family. The first executed replication will supply measured timing. Records without an assay match currently receive a zero-hour model value.","status":"unverified","severity":"high"},{"code":"signal_score_without_citations","basis":["5,529 of 5,529 records (100.0%) have no citation count from the source metadata."],"claim":"Signal score","gloss":"The signal score uses publication-type weight because the mirror supplied zero citation counts.","detail":"The source supplied no citation counts for any record in this run, so the signal score is publication-type weight only. The citation term of the ranking is inert here, and the shortlist is ordered by publication type alone.","status":"unverified","severity":"high"},{"code":"abstract_absent","basis":["1,667 of 5,529 records (30.2%) carry no abstract at all."],"claim":"Evidence base for classification","gloss":"Some records contain a title and publication type only, defining the available classification evidence.","detail":"Where the mirror contains a title and publication types only, those fields define the classifier evidence. A methods section is required for fuller automated and human review.","status":"unverified","severity":"medium"},{"code":"classifier_agreement_measured","basis":["Published two-way decision agreement 77.7% (310 of 399 decidable records) from a stratified hand-check of 438 real records.","Three-way diagnostic agreement 73.9% (288 of 390 decidable records).","data_only agreement 75.2% (100 of 133 decidable).","48 record(s) could not be decided from title and abstract and were excluded from the denominator.","56 analysis-only records were published under another work type, so the data_only share is not an upper bound."],"claim":"Published automatable decision","gloss":"This figure has been checked against a human reading the same papers, so we know how often it is right.","detail":"The published automatable / not-automatable distribution comes from a rule-based classifier that was hand-checked against a fixed ground-truth definition. The agreement rates below are measured, not estimated. The three-way work type remains a diagnostic and is reported separately.","status":"measured","severity":"high"},{"code":"llm_comparison_not_measured","basis":["rule_based_v1+lex99e1195c7d6f produced 5,529 of 5,529 classifications.","Measured on 438 labelled records; these are RULE-BASED figures, not model results."],"claim":"Rule-based versus LLM agreement","gloss":"Every number here is the rule engine’s own. Model comparison begins when a working API credential is connected and measured.","detail":"The published two-way decision agreed with a human reading on 310 of 399 decidable records (77.7%). The diagnostic three-way label agreed on 288 of 390 decidable records (73.9%). Every percentage in this run belongs to the rule engine. Model comparison begins when a working API credential is connected and measured.","status":"not_measured","severity":"high"},{"code":"confidence_is_a_band","basis":["low band: 135 of 210 hand-judged records were correct, 64.3% [57.6, 70.5] (95% CI).","medium band: 80 of 104 hand-judged records were correct, 76.9% [68.0, 84.0] (95% CI).","high band: 73 of 76 hand-judged records were correct, 96.0% [89.0, 98.7] (95% CI).","A fitted calibrated probability was built, measured and withdrawn: it overstated held-out accuracy and reorders nothing."],"claim":"Confidence band and evidence score","gloss":"The confidence band carries a measured accuracy interval; 0.85 represents relative rank strength.","detail":"Confidence on this run is a BAND plus its measured accuracy interval. The number stored alongside each record is a monotone evidence score that orders records; 0.85 represents relative rank strength. A fitted probability was withdrawn after it overstated held-out accuracy. Threshold on the band.","status":"measured","severity":"medium"},{"code":"three_way_split_is_diagnostic","basis":["The corpus is published at the two-way decision: automatable or not-automatable. The three-way split (data_only / physical / mixed) is published as a diagnostic with its measured reliability attached, not as a claim, because the rule engine's `mixed` call cannot be defended.","The engine called 22 record(s) mixed; 10 matched the human judgement (45.5%, 95% CI 26.9-65.3).","The engine's `mixed` call is right on 10/22 hand-judged records (45.5%, 95% CI 26.9%-65.3%); a constant `physical` guess scores 36.4%.","The engine's `mixed` call does not reliably beat a constant `physical` guess on the hand-judged records it labels mixed.","The sign of that difference flips between two independent samples, so the three-way refinement is not demonstrably informative.","The mixed stratum contributes a disproportionate share of errors relative to its size.","At title-only depth the physical/mixed split collapses: a title says that work was done, not whether it was also analysed."],"claim":"The published decision is two-way","gloss":"The three-way split is shown for diagnosis only. The published split is two ways.","detail":"Count and filter the corpus on automatable versus not-automatable. The data_only / physical / mixed split remains an internal engine diagnostic because the mixed call has lower measured reliability.","status":"measured","severity":"medium"},{"code":"automatable_flag_unproven","basis":["6 of 29 assay families are marked automatable now: meta_analysis, machine_learning, survival_analysis, pca, molecular_docking, differential_expression.","The flag is a rule over assay family and work type; validation begins with the first executed replication.","It inherits the 75.2% data_only agreement rate, because the flag requires the record to be analysis-only."],"claim":"Automatable now","gloss":"This flag marks assay families the rules classify as data-only. The first executed replication will validate it.","detail":"This flag marks families the rules consider replicable from data alone. Its validity depends on the analysis-only classification and will be measured through an executed replication.","status":"unverified","severity":"medium"}],"confidence_policy":"band_with_measured_interval","confidence_contract":{"policy":"band_with_measured_interval","summary":"Confidence is reported as a BAND with a measured accuracy interval. The raw evidence score supplies monotone ordering. A fitted point estimate was withdrawn after it overstated held-out accuracy.","evidence_score":"A monotone evidence score in [0,1] built from cue mass, axis separation and text coverage. Use it to order records. Interpret 0.85 as relative rank strength.","confidence_band":"low | medium | high. Consumers threshold on this value.","band_accuracy":"Wilson 95% interval on the measured agreement of the hand-judged records in this band.","calibrated_confidence":"WITHDRAWN. Reintroduction requires held-out evidence demonstrating reliable estimates across every bin."},"band_accuracy":{"low":{"n":210,"low":0.576,"band":"low","high":0.7046,"agree":135,"accuracy":0.6429},"high":{"n":76,"low":0.8903,"band":"high","high":0.9865,"agree":73,"accuracy":0.9605},"medium":{"n":104,"low":0.6795,"band":"medium","high":0.8397,"agree":80,"accuracy":0.7692}},"provider":"rule_based_v1+lex99e1195c7d6f","lexicon_id":"99e1195c7d6f","contract_published_at":"2026-10-23T12:25:29.022232+00:00","confidence_is_band":true,"confidence_is_probability":false,"decision_taxonomy":"two_way","decidable_fraction_two_way":0.8854,"decidable_fraction_two_way_low":0.8565,"decidable_fraction_two_way_high":0.9143,"decidable_fraction_three_way":0.8586,"decidable_fraction_three_way_low":0.8287,"decidable_fraction_three_way_high":0.8884,"decidable_population":5529,"validation_sample_size":438,"three_way_cost_fraction":0.0268,"three_way_cost_records":148,"decision_counts":{"automatable":230,"not_automatable":5299},"decision_split":{"automatable":{"count":230,"share":0.04159884246699222},"not_automatable":{"count":5299,"share":0.9584011575330078}},"diagnostic_work_type_counts":{"mixed":24,"physical":5275,"data_only":230}}}