ArticleJournal of experimental & clinical cancer research : CR2019
FBXO22 promotes the development of hepatocellular carcinoma by regulating the ubiquitination and degradation of p21.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 114 citations in OpenAlex.
- Preclinical evaluation and mechanistic analysis of antitumor effects of the novel anti-CD147 antibody DS-1471a in liver cancer models.Investigational new drugs · 2026Article
- Aryl Aldehyde-Anchored Small Molecules Recruit FBXO22 for Targeted Degradation of NSD2.Journal of medicinal chemistry · 2026Article
- Subcellular compartmentalization dependent dichotomy of p21 in cancer.Molecular biology reports · 2026Review
- Reduced FBXO22 skews human trophoblast fate equilibrium toward syncytialization via polyubiquitinating the CoREST complex.Nucleic acids research · 2026Article
- FBXO22 targets ubiquitination and degradation of c-Cbl in leukemia.Scientific reports · 2026Article
- FBXO22 promotes hepatocellular carcinoma progression via paracrine myo‑inositol‑induced M2‑type polarization of macrophages.International journal of molecular medicine · 2026Article
- Ubiquitination mediated by RING-type E3 ligases in the progression of digestive system tumors: mechanistic insights and potential therapeutic strategies.Frontiers in cell and developmental biology · 2026Review
- MicroRNAs as the critical regulators of ubiquitin-proteasome system through F-box protein targeting during tumor progression.Cancer cell international · 2025Review
- WWP2-induced inhibition of hepatocellular carcinoma cellular senescence via the ubiquitination and degradation of p21.Cell death & disease · 2025Article
- Review
- m6A regulators-based gene expression pattern is associated with immune microenvironment characteristics in hepatocellular carcinoma.Scientific reports · 2025Article
- F-box proteins in cancer: from cancer cells to the tumor microenvironment.Cell communication and signaling : CCS · 2025Review
- USP7-mediated stabilization of CXCL3 aggravates inflammation in models of acute lung injury.Journal of thoracic disease · 2025Article
- FBXO22 Suppresses Oxidative Stress-Induced ASK1 Activation and Cell Death via Ubiquitination-Dependent Degradation of TRIM48.International journal of molecular sciences · 2025Article
- ARHGAP4/MYH9/β-catenin/c-Jun positive feedback loop promotes colorectal cancer stemness.NPJ precision oncology · 2025Article
- FBXO10 inhibits ferroptosis and promotes the progression of esophageal squamous cell carcinoma by post-translational mediation of ACSL4 degradation.Journal of molecular histology · 2025Article
- E3 ligase TRIM22 promotes melanoma proliferation by regulating cell cycle progression through K63-linked ubiquitination of p21.Scientific reports · 2025Article
- FBXO22 deficiency defines a pleiotropic syndrome of growth restriction and multi-system anomalies associated with a unique epigenetic signature.American journal of human genetics · 2025Article
- F-box protein 22: A prognostic biomarker for colon cancer associated with immune infiltration and chemotherapy resistance.World journal of gastrointestinal oncology · 2025Article
- Death associated protein like 1 acts as a novel tumor suppressor in melanoma by increasing the stability of P21 protein.Molecular and cellular biochemistry · 2025Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundDeregulation of ubiquitin ligases is related to the malignant progression of human cancers. F-box only protein 22 (FBXO22), an F-box E3 ligase, is a member of the F-box protein family. However, the biological function of FBXO22 in HCC and the underlying molecular mechanisms are still unclear. In this study, we explored the role of FBXO22 in HCC and its mechanism of promoting tumor development.
methodsWe examined the expression of FBXO22 in normal liver cell lines, HCC cell lines, HCC tissue microarrays and fresh specimens. The correlation between FBXO22 and clinical features was analyzed in a retrospective study of 110 pairs of HCC tissue microarrays. Univariate and multivariate survival analyses were used to explore the prognostic value of FBXO22 in HCC. At the same time, the correlation between the FBXO22 and p21 was also studied in HCC samples. Knock-down and overexpression experiments, CHX and Mg132 intervention experiments, ubiquitination experiments, rescue experiments and nude mouse xenograft models were used to determine the potential mechanism by which FBXO22 promotes tumorigenesis in vitro and in vivo.
resultsThe expression of FBXO22 in HCC tissues was significantly higher than in normal liver tissues. The overall survival rate and disease-free survival time of patients with high expression of FBXO22 were significantly shorter than those of patients with low expression of FBXO22. The high expression of FBXO22 in HCC tissues were significantly correlated with serum AFP (p = 0. 003, Pearson's chi-squared test), tumor size (p = 0. 019, Pearson's chi-squared test) and vascular invasion (p = 0. 031, Pearson's chi-squared test). Especially, Multivariate analysis showed that tumor size and the expression of FBXO22 were independent prognostic indicator of OS (95% CI: 1.077-5.157, P<0.05). Correlation analysis also showed that FBXO22 was negatively correlated with p21 in tissue microarrays (r = - 0.3788, P<0.001, Pearson correlation) and fresh specimens (r = - 0.4037, P<0.01, Pearson correlation). Moreover, both in vitro and in vivo experiments showed that knocking down FBXO22 expression could inhibit cell proliferation, while overexpression of FBXO22 promoted tumor formation. Furthermore, we identified that FBXO22 interacts with p21 by regulating protein stability and by influencing the ubiquitination process. A knockdown of FBXO22 decreased the ubiquitylation of p21, while overexpression enhanced it.
conclusionsThis study uncovered a new mechanism by which FBXO22 functions as an oncogene in HCC pathogenesis and progression by mediating the ubiquitination and degradation of p21. It was also found that tumor size and the expression of FBXO22 were independent prognostic indicator of OS and the expression of FBXO22 and p21 was negatively correlated in clinical samples. Our findings present a new perspective for understanding the development of HCC, which may provide a new target for the treatment and management of this challenging cancer.
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