NUSAP1 Could be a Potential Target for Preventing NAFLD Progression to Liver Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35431924", "kind": "science-record", "revision": 5, "content_hash": "sha256:0ccc45bf978bc3a1eb645f47632737abde109eaf29b22fb16d9ba4eb765988da", "created_at": "2026-11-01T18:14:15Z", "updated_at": "2026-11-01T22:48:51Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "NUSAP1 Could be a Potential Target for Preventing NAFLD Progression to Liver Cancer.", "doi": "10.3389/fphar.2022.823140", "pmid": "35431924", "authors": ["Taofei Zeng", "Guanglei Chen", "Xinbo Qiao", "Hui Chen", "Lisha Sun", "Qingtian Ma", "Na Li", "Junqi Wang", "Chaoliu Dai", "Feng Xu"], "journal": "Frontiers in pharmacology", "year": 2022, "abstract": "Background: Non-alcoholic fatty liver disease (NAFLD) has gradually emerged as the most prevalent cause of chronic liver diseases. However, specific changes during the progression of NAFLD from non-fibrosis to advanced fibrosis and then hepatocellular carcinoma (HCC) are unresolved. Here, we firstly identify the key gene linking NAFLD fibrosis and HCC through analysis and experimental verification. Methods: Two GEO datasets (GSE89632, GSE49541) were performed for identifying differentially expressed genes (DEGs) associated with NAFLD progression from non-fibrosis to early fibrosis and eventually to advanced fibrosis. Subsequently, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis, protein-protein interaction (PPI) network were integrated to explore the potential function of the DEGs and hub genes. The expression of NUSAP1 was confirmed in vivo and in vitro NAFLD models at mRNA and protein level. Then, cell proliferation and migration under high fat conditions were verified by cell counting kit-8 (CCK-8) and wound-healing assays. The lipid content was measured with Oil Red O staining. Finally, the analysis of clinical survival curves was performed to reveal the prognostic value of the crucial genes among HCC patients via the online web-tool GEPIA2 and KM plotter. Results: 5510 DEGs associated with non-fibrosis NAFLD, 3913 DEGs about NAFLD fibrosis, and 739 DEGs related to NAFLD progression from mild fibrosis to advanced fibrosis were identified. Then, a total of 112 common DEGs were found. The result of enrichment analyses suggested that common DEGs were strongly associated with the glucocorticoid receptor pathway, regulation of transmembrane transporter activity, peroxisome, and proteoglycan biosynthetic process. Six genes, including KIAA0101, NUSAP1, UHRF1, RAD51AP1, KIF22, and ZWINT, were identified as crucial candidate genes via the PPI network. The expression of NUSAP1 was validated highly expressed in vitro and vivo NAFLD models at mRNA and protein level. NUSAP1 silence could inhibit the ability of cell proliferation, migration and lipid accumulation in vitro. Finally, we also found that NUSAP1 was significantly up-regulated at transcriptional and protein levels, and associated with poor survival and advanced tumor stage among HCC patients. Conclusion: NUSAP1 may be a potential therapeutic target for preventing NAFLD progression to liver cancer.", "claims": [{"id": "claim-method", "statement": "The “limma” software package in R software was used to screen out DEGs based on the cut-off criteria (Ritchie et al., 2015). The conditions of |log2 FC| ≥ 0.5, adjust p-value < 0.05 (corrected by B and H method) was used for NAFLD without fibrosis vs. healthy liver sample and NAFLD with fibrosis vs. healthy liver sample group to obtain DEGs associated with NAFLD fibrosis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35431924", "locator": "sections[4] \"DEGs Identification\" paragraph 2", "quote": "The “limma” software package in R software was used to screen out DEGs based on the cut-off criteria (Ritchie et al., 2015). The conditions of |log2 FC| ≥ 0.5, adjust p-value < 0.05 (corrected by B and H method) was used for NAFLD without fibrosis vs. healthy liver sample and NAFLD with fibrosis vs. healthy liver sample group to obtain DEGs associated with NAFLD fibrosis."}], "state": "complete"}, {"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:35431924", "locator": "sections[27] \"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"}, {"id": "claim-target-result", "statement": "Increased NUSAP1 mRNA levels were associated with shortened OS, RFS, PFS and DFS in HCC (p < 0.05).", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "In addition, the Kaplan-Meier curve and log-rank test analyses revealed that the increased NUSAP1 mRNA levels corresponded to the shortened OS (overall survival), RFS (relapse free survival), PFS (progression free survival) and DFS (distance free survival) in HCC (p < 0.05) (Figures 8C–G)."}, "evidence": [{"asset": "source:pmid:35431924", "locator": "sections[23] \"NUSAP1 Correlated With Poorer Prognosis in Liver Cancer\" paragraph 2", "quote": "In addition, the Kaplan-Meier curve and log-rank test analyses revealed that the increased NUSAP1 mRNA levels corresponded to the shortened OS (overall survival), RFS (relapse free survival), PFS (progression free survival) and DFS (distance free survival) in HCC (p < 0.05) (Figures 8C–G)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Increased NUSAP1 mRNA levels were associated with shortened OS, RFS, PFS and DFS in HCC (p < 0.05).", "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:35431924"], "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:GSE164441"], "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": {"fold_change": "value and absolute log2 fold-change cutoffs"}, "inputs": ["data:geo:GSE164441"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35431924", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fphar.2022.823140", "sha256": "sha256:3d037f93a2a39a0a1289237d0973b3dd53eba644e83b36d173bc6161343e7167", "bytes": 45552, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fphar.2022.823140", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9010788", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE164441", "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=GSE164441", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE164441", "version": null, "note": "The datasets presented in this study can be found in online repositories. 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The expression of NUSAP1 was confirmed in vivo and in vitro NAFLD models at mRNA and protei", "le Collection After 12 weeks’ treatment, the mice were sacrificed under deeply anesthesia. The livers were the", "le Collection After 12 weeks’ treatment, the mice were sacrificed under deeply anesthesia. The live"], "order_basis": "paper_text_order:934", "id": "assay:1"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["itions were verified by cell counting kit-8 (CCK-8) and wound-healing assays. The lipid content"], "order_basis": "paper_text_order:1098", "id": "assay:2"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["iCell Bioscience Inc., Shanghai, China) were cultured in a humidified incubator at 37 °C with 5% CO2", "cell model, HL-7702 and MHCC-97H cells were cultured in the presence or absence of 1 mmol/L free fat"], "order_basis": "paper_text_order:2632", "id": "assay:3"}, {"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": ["The “limma” software package in R software was used to screen out DEGs based on the cut-off criteria (Ritchie et al., 2015). The conditions of |log2 FC| ≥ 0.5, adjust p-value < 0.05 (corrected by B and H method) was used for NAFLD without fibrosis vs. healthy liver sample and NAFLD with fibrosis vs. healthy liver sample group to obtain DEGs associated with NAFLD fibrosis."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}