Aberrant SPOP-CHAF1A ubiquitination axis triggers tumor autophagy that endows a therapeutical vulnerability in diffuse large B cell lymphoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35773729", "kind": "science-record", "revision": 4, "content_hash": "sha256:0c641631b87056926bcc088fba90026c3daabf6713b0be9fc94905ddce7f57b8", "created_at": "2026-11-01T18:14:48Z", "updated_at": "2026-11-01T22:06:54Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Aberrant SPOP-CHAF1A ubiquitination axis triggers tumor autophagy that endows a therapeutical vulnerability in diffuse large B cell lymphoma.", "doi": "10.1186/s12967-022-03476-7", "pmid": "35773729", "authors": ["Wei Yan", "Xue Shi", "Huihan Wang", "Aijun Liao", "Wei Yang"], "journal": "Journal of translational medicine", "year": 2022, "abstract": "PURPOSE: Aberrant epigenetic changes, like DNA methylation, histone modifications, or ubiquitination, could trigger metabolic disorders in human cancer cells. This study planed to uncover the biological roles of epigenetic SPOP/CHAF1A axis in modulating tumor autophagy during Diffuse large B-cell lymphoma (DLBCL) tumorigenesis.\nMATERIALS AND METHODS: The Immunohistochemistry (IHC) was performed to assess the CHAF1A expressions. The expression data of CHAF1A was derived from The Cancer Genome Atlas (TCGA), GSE32918 and GSE83632 datasets. Bioinformatic assays contain differential analysis, functional enrichment analysis and Kaplan-Meier survival curve analysis. The colony generation assay, Transwell assay and CCK-8 assays were conducted for the in vitro assays. The in vivo ubiquitination assays were used to assess regulations of SPOP on CHAF1A. The Chromatin immunoprecipitation (ChIP) assays were used to uncover epigenetic regulations of CHAF1A on TFEB. The relevant DLBCL cells were subcutaneously injected to SCID beige mice to establish the xenograft models.\nRESULTS: Bioinformatic results revealed that CHAF1A expressed highly in DLBCL that were validated in patients samples. Patients with high CHAF1A suffered from inferior prognosis with shorter survival months relative to those with low CHAF1A. High CHAF1A enhanced DLBCL aggressiveness, including cell proliferation, migration and in vivo growth. Mechanistically, E3 ubiquitin ligase SPOP binds to and induces the degradative ubiquitination of CHAF1A via recognizing a consensus SPOP-binding motif in CHAF1A. SPOP is down-regulated in DLBCL and habours two DLBCL-associated mutations. Deficient SPOP leads to accumulated CHAF1A proteins that promote malignant features of DLBCL. Subsequently, ChIP-qPCR assay revealed that CHAF1A directly binds to TFEB promoters to activate the expressions. High CHAF1A could enhance the transcriptional activity of TFEB and downstream genes. The SPOP/CHAF1A axis modulates TFEB-dependent transactivation to regulate the lysosomal biogenesis and autophagy. The in vivo models suggested that TFEB inhibition is effective to suppress growth of SPOP-deficient DLBCLs.\nCONCLUSIONS: CHAF1A is aberrantly elevated in SPOP-deficient DLBCL. The in-depth mechanism understanding of SPOP/CHAF1A/TFEB axis endows novel targets for DLBCL treatment.", "claims": [{"id": "claim-method", "statement": "Bioinformatic assays contain differential analysis, functional enrichment analysis and Kaplan–Meier survival curve analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35773729", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Bioinformatic assays contain differential analysis, functional enrichment analysis and Kaplan–Meier survival curve analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The molecular experiment data generated and analyzed during the current study are available from the corresponding author with the reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35773729", "locator": "sections[26] \"Data availability\" paragraph 2", "quote": "The molecular experiment data generated and analyzed during the current study are available from the corresponding author with the reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Based on the DLBCL samples (N = 249) in GSE32918 from the GEO database, we conducted the Kaplan–Meier survival curve analysis and found that high CHAF1A levels correlated with shorter overall survival (OS) months in contrast to those patients with low CHAF1A (log-rank test P = 0.011, Fig. 1E).", "kind": "quantitative", "target": {"value": 0.011, "unit": "p-value", "tolerance": null, "source": "Based on the DLBCL samples (N = 249) in GSE32918 from the GEO database, we conducted the Kaplan–Meier survival curve analysis and found that high CHAF1A levels correlated with shorter overall survival (OS) months in contrast to those patients with low CHAF1A (log-rank test P = 0.011, Fig. 1E)."}, "evidence": [{"asset": "source:pmid:35773729", "locator": "sections[17] \"High CHAF1A in DLBCL is a prognostic factor and correlates with poor prognosis\" paragraph 2", "quote": "Based on the DLBCL samples (N = 249) in GSE32918 from the GEO database, we conducted the Kaplan–Meier survival curve analysis and found that high CHAF1A levels correlated with shorter overall survival (OS) months in contrast to those patients with low CHAF1A (log-rank test P = 0.011, Fig. 1E)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Based on the DLBCL samples (N = 249) in GSE32918 from the GEO database, we conducted the Kaplan–Meier survival curve analysis and found that high CHAF1A levels correlated with shorter overall survival (OS) months in contrast to those patients with low CHAF1A (log-rank test P = 0.011, Fig. 1E).", "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:35773729"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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MATERIALS AND METHODS: The Immunohistochemistry (IHC) was performed to assess the CHAF1A exp", "RIALS AND METHODS: The Immunohistochemistry (IHC) was performed to assess the CHAF1A expressi"], "order_basis": "paper_text_order:454", "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": ["colony generation assay, Transwell assay and CCK-8 assays were conducted for the in vitro assay"], "order_basis": "paper_text_order:814", "id": "assay:2"}, {"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": ["were conducted for the in vitro assays. 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