Knockdown of AKR1C3 Promoted Sorafenib Sensitivity Through Inhibiting the Phosphorylation of AKT in Hepatocellular Carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35359392", "kind": "science-record", "revision": 5, "content_hash": "sha256:b2903d217c0c47330bd061a4960cc1bee85b6dd7d812a3d4fbeb955ce3345e8d", "created_at": "2026-11-01T18:14:09Z", "updated_at": "2026-11-01T22:48:45Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Knockdown of AKR1C3 Promoted Sorafenib Sensitivity Through Inhibiting the Phosphorylation of AKT in Hepatocellular Carcinoma.", "doi": "10.3389/fonc.2022.823491", "pmid": "35359392", "authors": ["Jia Zheng", "Zhihong Yang", "Yanlei Li", "Li Yang", "Ruili Yao"], "journal": "Frontiers in oncology", "year": 2022, "abstract": "Background: Sorafenib, which can induce ferroptosis, is a multikinase inhibitor for enhancing survival in advanced hepatocellular carcinoma (HCC). However, a considerable challenge for the treatment of HCC is sorafenib resistance. Therefore, targeting the relationship between sorafenib resistance and ferroptosis genes may provide a novel approach for the treatment of HCC.\nMaterials and Methods: We analyzed the gene expression and clinicopathological factors from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO) databases (GSE109211/GSE62813). The statistical analysis was conducted in R. Cell proliferation was assayed by MTT, cell colony-forming assay, and wound healing assay. Immunofluorescence assay and Western blot were used to evaluate the expression of AKT.\nResults: Many ferroptosis-related genes were upregulated in the sorafenib-resistant group. Aldo-keto reductase 1C3 (AKR1C3) was highly expressed in sorafenib-resistant patients, and the high expression of AKR1C3 was associated with the poor prognosis of patients from the TCGA and ICGC databases. MTT and colony-forming assays showing AKR1C3 overexpression enhanced the proliferation of HCC cells and acute sorafenib resistance. Knockdown of AKR1C3 inhibited the proliferation of HCC cells and increased the drug sensitivity of sorafenib. Immunofluorescence assay and Western blot proved that AKR1C3 promoted the phosphorylation of AKT.\nConclusion: AKR1C3 can induce sorafenib resistance through promoting the phosphorylation of AKT in HCC. AKR1C3 inhibitors may be used in conjunction with sorafenib to become a better therapeutic target for HCC.", "claims": [{"id": "claim-method", "statement": "The raw data were standardized and analyzed by the R package “limma” from the Bioconductor project.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35359392", "locator": "sections[3] \"Bioinformatic Analysis\" paragraph 2", "quote": "The raw data were standardized and analyzed by the R package “limma” from the Bioconductor project."}], "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:35359392", "locator": "sections[19] \"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": "AKR1C3 can induce sorafenib resistance through promoting the phosphorylation of AKT in HCC.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35359392", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "AKR1C3 can induce sorafenib resistance through promoting the phosphorylation of AKT in HCC."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "AKR1C3 can induce sorafenib resistance through promoting the phosphorylation of AKT in HCC.", "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:35359392"], "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:GSE109211"], "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:GSE109211"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35359392", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fonc.2022.823491", "sha256": "sha256:c748c2096f0fc087b0365632c3f6bfec0e252a4967f074b82a02ddbe6696034c", "bytes": 28404, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fonc.2022.823491", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8963762", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE109211", "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=GSE109211", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE109211", "version": null, "note": "The datasets presented in this study can be found in online repositories. 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Knockdown of AKR1C3 inhibited the proliferation of HCC"], "order_basis": "paper_text_order:0", "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": 0.99, "evidence": ["cted in R. Cell proliferation was assayed by MTT, cell colony-forming assay, and wound healin", "f patients from the TCGA and ICGC databases. MTT and colony-forming assays showing AKR1C3 ove"], "order_basis": "paper_text_order:808", "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": ["lony-forming assay, and wound healing assay. 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Immunofluorescence assay and Western blot proved that AKR1C3 promoted the phosphorylat"], "order_basis": "paper_text_order:895", "id": "assay:4"}, {"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": ["or Biological Sciences (Shanghai, China) and cultured in Dulbecco’s modified Eagle’s medium (DMEM, Hy", "nsduction Human hepatoma cell lines Huh7 and HepG2 were obtained from the Chinese Academy of Sc"], "order_basis": "paper_text_order:1873", "id": "assay:5"}, {"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 raw data were standardized and analyzed by the R package “limma” from the Bioconductor project."], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}