ArticleJournal of physiology and biochemistry2024
TAF15 inhibits p53 nucleus translocation and promotes HCC cell 5-FU resistance via post-transcriptional regulation of UBE2N.
Article in Journal of physiology and biochemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Exportin 1 inhibitor KPT‑330 reverses oxaliplatin resistance via p53 nuclear retention in colorectal cancer.International journal of molecular medicine · 2026Article
- Nanobody Nb07 mitigates sepsis by blocking the PFKM-p53-PD-1 axis to enhance macrophage phagocytosis.Theranostics · 2026Article
- Mechanisms of drug resistance in hepatocellular carcinoma.Biological procedures online · 2025Review
- UBE2N as a novel prognostic and therapeutic biomarker of lung adenocarcinoma.Frontiers in immunology · 2025Article
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Authors and funding
6 authors.
Funding
Abstract
Chemotherapy resistance is an important factor responsible for the low 5-year survival rate of hepatocellular carcinoma (HCC) patients. Ubiquitin-conjugating enzyme E2N (UBE2N) is a cancer-associated ubiquitin-conjugating enzyme that is expressed in HCC tissues, and its high expression is associated with a poor prognosis. This study explored the role played by UBE2N in development of 5-fluorouracil (5-FU) resistance in HCC cells. Three HCC cell lines (HepG2 [p53 wild type], Huh7 [p53 point mutant type], Hep3B [p53 non-expression type]), and one normal liver cell line (MIHA) were used in our present study. The IC50 value of 5-FU was determined using a cell counting kit-8 (CCK-8) assay. Cell viability was assessed by colony formation assays. TUNEL assays and flow cytometry were used to analyze cell apoptosis. RNA pull-down and RNA immunoprecipitation (RIP) assays were performed to confirm the binding relationship between UBE2N mRNA and TAF15 protein. Our results showed that TAF15 and UBE2N were highly expressed in HCC cells. UBE2N inhibited the translocation of p53 protein into the cell nucleus to increase 5-FU resistance, as reflected by an increased IC50 value, an increase in cell viability, and a reduction in cell apoptosis. Overexpression of p53 reduced 5-FU resistance, but that effect could be reversed by UBE2N overexpression. TAF15 protein bound to and stabilized UBE2N mRNA, thereby inhibiting p53 translocation into the nucleus and promoting 5-FU resistance in HCC cells. Collectively, our present study identified a novel mechanism by which TAF15/UBE2N regulates p53 distribution to increase 5-FU resistance. Our results also suggest potential therapeutic strategies for treating HCC.
Indexed as
Identifiers
39446246What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.