ArticleHepatology (Baltimore, Md.)2020
Depletion of TRRAP Induces p53-Independent Senescence in Liver Cancer by Down-Regulating Mitotic Genes.
Article in Hepatology (Baltimore, Md.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 74 citations in OpenAlex.
- KRAS Withdrawal in Cholangiocarcinoma Leads to Immune Infiltration and Tumor Regression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Construction of circadian clock signature for tumor microenvironment in predicting survival of esophageal squamous cell carcinoma.Frontiers in immunology · 2026Article
- SRSF3 knockdown-induced cellular senescence as a possible therapeutic strategy for non-small cell lung cancer.Carcinogenesis · 2025Article
- Antagonism of the ATP-gated P2X7 receptor inhibits the proliferation of hepatocellular carcinoma cells.Purinergic signalling · 2025Article
- A CHD8-TRRAP axis facilitates MYC and E2F target gene regulation in human neural stem cells.iScience · 2025Article
- Bioengineered extracellular vesicles: The path to precision medicine in liver diseases.Liver research (Beijing, China) · 2025Review
- USP9X deubiquitinates TRRAP to promote glioblastoma cell proliferation and migration and M2 macrophage polarization.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Creation of an innovative diagnostic framework for hepatocellular carcinoma employing bioinformatics techniques focused on senescence-related and pyroptosis-related genes.Frontiers in oncology · 2025Article
- Inhibition of lung tumorigenesis by transient reprogramming in cancer cells.Cell death & disease · 2024Article
- DNA Damage and Inflammatory Response of p53 Null H358 Non-Small Cell Lung Cancer Cells to X-Ray Exposure Under Chronic Hypoxia.International journal of molecular sciences · 2024Article
- Review
- A genome-wide study of gastric intramucosal neoplasia based on somatic copy number alterations, gene mutations, and mRNA expression patterns.The journal of pathology. Clinical research · 2024Article
- TRIM22 induces cellular senescence by targeting PHLPP2 in hepatocellular carcinoma.Cell death & disease · 2024Article
- CRISPR in Targeted Therapy and Adoptive T Cell Immunotherapy for Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2024Review
- EZH2-H3K27me3-mediated silencing of mir-139-5p inhibits cellular senescence in hepatocellular carcinoma by activating TOP2A.Journal of experimental & clinical cancer research : CR · 2023Article
- Review
- DHX37 Is a Promising Prognostic Biomarker and a Therapeutic Target for Immunotherapy and Chemotherapy in HCC.Cancers · 2023Article
- [Screening and validation of pivotal genes in hepatitis B virus-associated hepatocellular carcinoma].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2023Article
- Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies.MedComm · 2023Review
- The CRISPR/Cas9 System Delivered by Extracellular Vesicles.Pharmaceutics · 2023Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Hepatocellular carcinoma (HCC) is an aggressive subtype of liver cancer with few effective treatments, and the underlying mechanisms that drive HCC pathogenesis remain poorly characterized. Identifying genes and pathways essential for HCC cell growth will aid the development of new targeted therapies for HCC. Using a kinome CRISPR screen in three human HCC cell lines, we identified transformation/transcription domain-associated protein (TRRAP) as an essential gene for HCC cell proliferation. TRRAP has been implicated in oncogenic transformation, but how it functions in cancer cell proliferation is not established. Here, we show that depletion of TRRAP or its co-factor, histone acetyltransferase KAT5, inhibits HCC cell growth through induction of p53-independent and p21-independent senescence. Integrated cancer genomics analyses using patient data and RNA sequencing identified mitotic genes as key TRRAP/KAT5 targets in HCC, and subsequent cell cycle analyses revealed that TRRAP-depleted and KAT5-depleted cells are arrested at the G2/M phase. Depletion of topoisomerase II alpha (TOP2A), a mitotic gene and TRRAP/KAT5 target, was sufficient to recapitulate the senescent phenotype of TRRAP/KAT5 knockdown. Conclusion: Our results uncover a role for TRRAP/KAT5 in promoting HCC cell proliferation by activating mitotic genes. Targeting the TRRAP/KAT5 complex is a potential therapeutic strategy for HCC.
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