ArticlePloS one2013
Different involvement of promoter methylation in the expression of organic cation/carnitine transporter 2 (OCTN2) in cancer cell lines.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 25 citations in OpenAlex.
- Dysfunction of the carnitine cycle in tumor progression.Heliyon · 2024Review
- The Human OCTN Sub-Family: Gene and Protein Structure, Expression, and Regulation.International journal of molecular sciences · 2024Review
- Inflammation and Organic Cation Transporters Novel (OCTNs).Biomolecules · 2024Review
- Clinical Significance of Carnitine in the Treatment of Cancer: From Traffic to the Regulation.Oxidative medicine and cellular longevity · 2023Review
- Article
- A guide to plasma membrane solute carrier proteins.The FEBS journal · 2021Review
- DNA Methylation-Based Epigenetic Repression of SLC22A4 Promotes Resistance to Cytarabine in Acute Myeloid Leukemia.Clinical and translational science · 2021Article
- Identification of hub methylated-CpG sites and associated genes in oral squamous cell carcinoma.Cancer medicine · 2020Article
- Intestinal OCTN2- and MCT1-targeted drug delivery to improve oral bioavailability.Asian journal of pharmaceutical sciences · 2020Review
- Carnitine Traffic in Cells. Link With Cancer.Frontiers in cell and developmental biology · 2020Review
- Characterization of Exosomal SLC22A5 (OCTN2) carnitine transporter.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Organic cation/carnitine transporter 2 (OCTN2) is responsible for the cellular uptake of the antineoplastic agent, oxaliplatin. Epigenetic modification is a possible mechanism of altered drug-transporter expression in cancers, leading to altered efficacy of chemotherapeutic drugs. However, the mechanisms governing OCTN2 regulation are not completely understood. In this study, the low levels of OCTN2 in HepG2 and LS174T cells were elevated by the demethylating reagent, decitabine (DCA). To further reveal the epigenetic mechanism of down-regulation of OCTN2, we found that Region-1 within the OCTN2 promoter (spanning -354 to +85) was a determinant of OCTN2 expression in a luciferase reporter assay. Moreover, methylation-specific PCR (MSP) and bisulfite genomic sequencing showed that the degree of individual methylated CpG sites within this region was inversely correlated with the levels of OCTN2 in different cancer cells. Application of DCA to HepG2 and LS174T cells reversed the hypermethylation status of the OCTN2 promoter and increased OCTN2 expression, enhancing cellular uptake of oxaliplatin. Thus, we identified that promoter methylation is responsible for epigenetic down-regulation of OCTN2 in HepG2 and LS174T cells. Given the essential role of OCTN2 in cancer cell uptake of chemotherapeutics, and thus treatment efficacy, pretreatment with a demethylating reagent is a possible strategy for optimizing pharmacotherapies against cancers.
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