ArticleThe Journal of biological chemistry2015
The Steroidogenic Enzyme AKR1C3 Regulates Stability of the Ubiquitin Ligase Siah2 in Prostate Cancer Cells.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 35 citations in OpenAlex.
- AKR1C3 Binds β-Trcp to Promote the Degradation of TFRC to Protect Hepatocellular Carcinoma From Ferroptosis.Cancer science · 2026Article
- AKR1C3-PKM2-oxidative phosphorylation axis drives prostate cancer radioresistance via UBE2T upregulation.Cell death & disease · 2026Article
- Identification of Pyroptosis-Related Molecular Subtypes and Diagnostic Model development in Major Depressive Disorder.Molecular biotechnology · 2025Article
- Article
- Article
- AKR1C3 in carcinomas: from multifaceted roles to therapeutic strategies.Frontiers in pharmacology · 2024Review
- Novel inhibition of AKR1C3 and androgen receptor axis by PTUPB synergizes enzalutamide treatment in advanced prostate cancer.Oncogene · 2023Article
- Functional roles of E3 ubiquitin ligases in prostate cancer.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Expression of AKR1C3, β-Catenin and LEF1 in Esophageal Squamous Cell Carcinoma and the Relationship with Radiation Resistance.Iranian journal of public health · 2021Article
- Targeting ADT-Induced Activation of the E3 Ubiquitin Ligase Siah2 to Delay the Occurrence of Castration-Resistant Prostate Cancer.Frontiers in oncology · 2021Article
- Histone demethylase JMJD1A promotes expression of DNA repair factors and radio-resistance of prostate cancer cells.Cell death & disease · 2020Article
- Intracrine androgen biosynthesis and drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2020Review
- AKR1C3 Promotes AR-V7 Protein Stabilization and Confers Resistance to AR-Targeted Therapies in Advanced Prostate Cancer.Molecular cancer therapeutics · 2019Article
- AKR1C3 (type 5 17β-hydroxysteroid dehydrogenase/prostaglandin F synthase): Roles in malignancy and endocrine disorders.Molecular and cellular endocrinology · 2019Review
- Consecutive Prostate Cancer Specimens Revealed Increased Aldo⁻Keto Reductase Family 1 Member C3 Expression with Progression to Castration-Resistant Prostate Cancer.Journal of clinical medicine · 2019Article
- Article
- Article
- Inhibition of AKR1C3 Activation Overcomes Resistance to Abiraterone in Advanced Prostate Cancer.Molecular cancer therapeutics · 2017Article
- Aldo-Keto Reductase AKR1C1-AKR1C4: Functions, Regulation, and Intervention for Anti-cancer Therapy.Frontiers in pharmacology · 2017Review
- Current advances in intratumoral androgen metabolism in castration-resistant prostate cancer.Current opinion in endocrinology, diabetes, and obesity · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Re-activation of androgen receptor (AR) activity is the main driver for development of castration-resistant prostate cancer. We previously reported that the ubiquitin ligase Siah2 enhanced AR transcriptional activity and prostate cancer cell growth. Among the genes we found to be regulated by Siah2 was AKR1C3, which encodes a key androgen biosynthetic enzyme implicated in castration-resistant prostate cancer development. Here, we found that Siah2 inhibition in CWR22Rv1 prostate cancer cells decreased AKR1C3 expression as well as intracellular androgen levels, concomitant with inhibition of cell growth in vitro and in orthotopic prostate tumors. Re-expression of either wild-type or catalytically inactive forms of AKR1C3 partially rescued AR activity and growth defects in Siah2 knockdown cells, suggesting a nonenzymatic role for AKR1C3 in these outcomes. Unexpectedly, AKR1C3 re-expression in Siah2 knockdown cells elevated Siah2 protein levels, whereas AKR1C3 knockdown had the opposite effect. We further found that AKR1C3 can bind Siah2 and inhibit its self-ubiquitination and degradation, thereby increasing Siah2 protein levels. We observed parallel expression of Siah2 and AKR1C3 in human prostate cancer tissues. Collectively, our findings identify a new role for AKR1C3 in regulating Siah2 stability and thus enhancing Siah2-dependent regulation of AR activity in prostate cancer cells.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.