ArticleJournal of experimental & clinical cancer research : CR2019
14-3-3ζ inhibits heme oxygenase-1 (HO-1) degradation and promotes hepatocellular carcinoma proliferation: involvement of STAT3 signaling.
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 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- Dihydromyricetin mitigates abdominal aortic aneurysmActa pharmaceutica Sinica. B · 2025Article
- The promoter T-413A variant and elevated enzyme levels of heme oxygenase-1 associated with an increased risk of polycystic ovarian syndrome.Frontiers in endocrinology · 2025Article
- 14-3-3ζ suppresses RANKL signaling by destabilizing TRAF6.The Journal of biological chemistry · 2024Article
- Characterization of dipyridamole as a novel ferroptosis inhibitor and its therapeutic potential in acute respiratory distress syndrome management.Theranostics · 2024Article
- Circ-VPS13C enhances cisplatin resistance in ovarian cancer via modulating the miR-106b-5p/YWHAZ axis.Archives of medical science : AMS · 2024Article
- KHDRBS3 accelerates glycolysis and promotes malignancy of hepatocellular carcinoma via upregulating 14-3-3ζ.Cancer cell international · 2023Article
- Article
- Non-canonical vs. Canonical Functions of Heme Oxygenase-1 in Cancer.Journal of cancer prevention · 2022Review
- Exploiting Interdata Relationships in Prostate Cancer Proteomes: Clinical Significance of HO-1 Interactors.Antioxidants (Basel, Switzerland) · 2022Article
- The non-canonical effects of heme oxygenase-1, a classical fighter against oxidative stress.Redox biology · 2021Review
- A hypoxia-linked gene signature for prognosis prediction and evaluating the immune microenvironment in patients with hepatocellular carcinoma.Translational cancer research · 2021Article
- Article
- Expression ofOncology letters · 2020Article
- Regulation of the Expression of Heme Oxygenase-1: Signal Transduction, Gene Promoter Activation, and Beyond.Antioxidants & redox signaling · 2020Review
- Overexpression of 14-3-3BioMed research international · 2020Article
- The role of YWHAZ in cancer: A maze of opportunities and challenges.Journal of Cancer · 2020Review
- Heme Oxygenase-1 Inhibition Sensitizes Human Prostate Cancer Cells towards Glucose Deprivation and Metformin-Mediated Cell Death.International journal of molecular sciences · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundHeme oxygenase 1 (HO-1) has been reported to be very important in the pathogenesis or progression of multiple types of cancer. Identification of novel hmox1 binding proteins may reveal undefined oncogenes, tumor suppressors, signaling pathways, and possible treatment targets.
methodsImmunoprecipitation and mass spectrometry analyses were used to identify novel regulators of HO-1. The association of the 14-3-3ζ protein with HO-1 and modulation of the stability of HO-1 were investigated by co-immunoprecipitation, immunofluorescence, western blotting, and quantitative RT-PCR. Degradation and in vivo ubiquitination assays were utilized to examine whether 14-3-3ζ stabilizes the HO-1 protein by inhibiting its ubiquitination. The effect of 14-3-3ζ on proliferation was investigated by function assays conducted in vitro using the CCK-8 and colony formation assays and in vivo in a xenograft mouse model. The biological functions of the 14-3-3ζ/HO-1 axis were demonstrated by western blotting and rescue experiments. Using gain-of-function and loss-of-function strategies, we further clarified the impact of 14-3-3ζ/HO-1 complex on the signal transducers and activators of transcription 3 (STAT3) signaling pathway in cancer cells.
resultsWe identified 14-3-3ζ as a novel HO-1 binding protein. The binding inhibited the ubiquitination and proteasome-mediated degradation of HO-1, thus facilitating its stabilization. Enforced expression of 14-3-3ζ significantly promoted cell proliferation in vitro, as well as tumorigenesis in vivo, while 14-3-3ζ knockdown had opposite effects. The data indicated that 14-3-3ζ can stabilize HO-1 expression and thus influence cancer cell proliferation. We further demonstrated the involvement of the STAT3 pathway in 14-3-3ζ/HO-1 regulation of hepatocellular carcinoma cell proliferation.
conclusionsCollectively, these data show that 14-3-3ζ regulates the stability of HO-1 to promote cancer cell proliferation and STAT3 signaling activation. The data establish the 14-3-3ζ-HO-1-STAT3 axis as an important regulatory mechanism of cancer cell growth and implicate HO-1 and 14-3-3ζ as potential therapeutic targets in hepatocellular carcinoma.
Indexed as
Identifiers
What 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.