TUBB2B facilitates progression of hepatocellular carcinoma by regulating cholesterol metabolism through targeting HNF4A/CYP27A1.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36872411", "kind": "science-record", "revision": 4, "content_hash": "sha256:c10fc41d2249b6d37b63c8b13494d20e546916bdd6789920d636513ec2138465", "created_at": "2026-11-01T19:01:30Z", "updated_at": "2026-11-01T22:51:25Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "TUBB2B facilitates progression of hepatocellular carcinoma by regulating cholesterol metabolism through targeting HNF4A/CYP27A1.", "doi": "10.1038/s41419-023-05687-2", "pmid": "36872411", "authors": ["Xiaobo Wang", "Jiawei Shi", "Mingming Huang", "Jiehong Chen", "Jia Dan", "Yunhua Tang", "Zhiyong Guo", "Xiaoshun He", "Qiang Zhao"], "journal": "Cell death & disease", "year": 2023, "abstract": "Cholesterol metabolism plays a critical role in the progression of hepatocellular carcinoma (HCC), but it is not clear how cholesterol metabolism is regulated. The tubulin beta class I genes (TUBBs) are associated with the prognosis of many different cancers. To confirm the function of TUBBs in HCC, the Kaplan-Meier method and Cox analyses were performed using TCGA and GSE14520 datasets. A higher expression of TUBB2B is an independent prognostic factor for shorter over survival in HCC patients. Deletion of TUBB2B in hepatocytes inhibits proliferation and promotes tumor cell apoptosis, while over-expression of TUBB2B has the opposite function. This result was confirmed in a mouse xenograft tumor model. Mechanistically, TUBB2B induces the expression of CYP27A1, an enzyme responsible for the conversion of cholesterol to 27-hydroxycholesterol, which leads to the up-regulation of cholesterol and the progression of HCC. In addition, TUBB2B regulates CYP27A1 via human hepatocyte nuclear factor 4alpha (HNF4A). These findings indicated that TUBB2B functions as an oncogene in HCC, and plays a role in promoting cell proliferation and anti-apoptosis through targeting HNF4A/CYP27A1/cholesterol.", "claims": [{"id": "claim-method", "statement": "Over survival (OS) was evaluated by the Kaplan–Meier (K-M) survival curve and the log-rank test. Prognostic factors were estimated using a univariate Cox proportional hazards regression model and a multivariate Cox model.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36872411", "locator": "sections[12] \"Statistical analysis\" paragraph 2", "quote": "Over survival (OS) was evaluated by the Kaplan–Meier (K-M) survival curve and the log-rank test. 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