ArticleScientific reports2017
Peretinoin, an acyclic retinoid, inhibits hepatocarcinogenesis by suppressing sphingosine kinase 1 expression in vitro and in vivo.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Retinoic acid in health and disease.Signal transduction and targeted therapy · 2026Review
- The SP1-SuperEnhancer-SPHK1 Axis Mediates Niraparib Resistance in TNBC.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Epigenetic drugs against human DNA viruses and retroviruses.Antiviral research · 2025Review
- Exploring the Anti-Leukemic Effect of the Synthetic Retinoid ST1926 on Malignant T Cells: A Comprehensive Proteomics Approach.International journal of molecular sciences · 2025Article
- SP1-Driven FOXM1 Upregulation Induces Dopaminergic Neuron Injury in Parkinson's Disease.Molecular neurobiology · 2024Article
- The emerging roles of sphingosine 1-phosphate and SphK1 in cancer resistance: a promising therapeutic target.Cancer cell international · 2024Review
- Identification of ligand and receptor interactions in CKD and MASH through the integration of single cell and spatial transcriptomics.PloS one · 2024Article
- Retinoid X receptor heterodimers in hepatic function: structural insights and therapeutic potential.Frontiers in pharmacology · 2024Review
- Integrative roles of sphingosine kinase in liver pathophysiology.Toxicological research · 2023Review
- Role of vitamins A, C, D, E in cancer prevention and therapy: therapeutic potentials and mechanisms of action.Frontiers in nutrition · 2023Review
- Retinoids as anti-cancer agents and their mechanisms of action.American journal of cancer research · 2022Review
- Targeting the Sphingosine Kinase/Sphingosine-1-Phosphate Signaling Axis in Drug Discovery for Cancer Therapy.Cancers · 2021Review
- Peretinoin, an Acyclic Retinoid, for the Secondary Prevention of Hepatocellular Carcinoma.Molecules (Basel, Switzerland) · 2021Review
- Omics-Based Identification of Shared and Gender Disparity Routes inFrontiers in genetics · 2021Article
- Risk Factors, Pathogenesis, and Strategies for Hepatocellular Carcinoma Prevention: Emphasis on Secondary Prevention and Its Translational Challenges.Journal of clinical medicine · 2020Review
- Review
- Targeting the SphK-S1P-SIPR Pathway as a Potential Therapeutic Approach for COVID-19.International journal of molecular sciences · 2020Review
- Discovery of Harmaline as a Potent Inhibitor of Sphingosine Kinase-1: A Chemopreventive Role in Lung Cancer.ACS omega · 2020Article
- Generation of mice with hepatocyte-specific conditional deletion of sphingosine kinase 1.Transgenic research · 2020Article
- Association Between Aspirin Use and Risk of Hepatocellular Carcinoma.JAMA oncology · 2018Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sphingosine-1-phospate is a potent bioactive lipid metabolite that regulates cancer progression. Because sphingosine kinase 1 and sphingosine kinase 2 (SPHK 1/2) are both essential for sphingosine-1-phospate production, they could be a therapeutic target in various cancers. Peretinoin, an acyclic retinoid, inhibits post-therapeutic recurrence of hepatocellular carcinoma via unclear mechanisms. In this study, we assessed effects of peretinoin on SPHK expression and liver cancer development in vitro and in vivo. We examined effects of peretinoin on expression, enzymatic and promoter activity of SPHK1 in a human hepatoma cell line, Huh-7. We also investigated effects of SPHK1 on hepatocarcinogenesis induced by diethylnitrosamine using SPHK1 knockout mice. Peretinoin treatment of Huh-7 cells reduced mRNA levels, protein expression and enzymatic activity of SPHK1. Peretinoin reduced SPHK1 promoter activity; this effect of peretinoin was blocked by overexpression of Sp1, a transcription factor. Deletion of all Sp1 binding sites within the SPHK1 promoter region abolished SPHK1 promoter activity, suggesting that peretinoin reduced mRNA levels of SPHK1 via Sp1. Additionally, diethylnitrosamine-induced hepatoma was fewer and less frequent in SPHK1 knockout compared to wild-type mice. Our data showed crucial roles of SPHK1 in hepatocarcinogenesis and suggests that peretinoin prevents hepatocarcinogenesis by suppressing mRNA levels of SPHK1.
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