ArticleHormones & cancer2014
1α,25-dihydroxyvitamin D3 modulates CYP2R1 gene expression in human oral squamous cell carcinoma tumor cells.
Article in Hormones & cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- The Impact of Vitamin D Levels on Inflammatory Status: A Systematic Review of Immune Cell Studies.PloS one · 2015Pooled it
- Vitamin D status, vitamin D receptor, CYP2R1, and CYP24A1 profiles in children.Frontiers in nutrition · 2024Article
- Editorial: The role of vitamin D as an immunomodulator.Frontiers in immunology · 2023Article
- Identification of Biomarkers Associated with Cancerous Change in Oral Leukoplakia Based on Integrated Transcriptome Analysis.Journal of oncology · 2022Article
- SPINK7 expression changes accompanied by HER2, P53 and RB1 can be relevant in predicting oral squamous cell carcinoma at a molecular level.Scientific reports · 2021Article
- Dysregulation of vitamin D synthesis pathway genes in colorectal cancer: A case-control study.Journal of clinical laboratory analysis · 2021Article
- Differential Expression of Prostaglandin I2 Synthase Associated with Arachidonic Acid Pathway in the Oral Squamous Cell Carcinoma.Journal of oncology · 2018Article
- Article
- Vitamin D Protects Against Atherosclerosis via Regulation of Cholesterol Efflux and Macrophage Polarization in Hypercholesterolemic Swine.Arteriosclerosis, thrombosis, and vascular biology · 2015Article
- Serum vitamin D levels of patients with oral squamous cell carcinoma (OSCC) and expression of vitamin D receptor in oral precancerous lesions and OSCC.Medicina oral, patologia oral y cirugia bucal · 2015Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oral squamous cell carcinomas (OSCC) are the most common malignant neoplasms associated with mucosal surfaces of the oral cavity and oropharynx. 1α,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is implicated as an anticancer agent. Cytochrome P450 2R1 (CYP2R1) is a microsomal vitamin D 25-hydroxylase which plays an important role in converting dietary vitamin D to active metabolite, 25-(OH)D3. We identified high levels of CYP2R1 expression using tissue microarray of human OSCC tumor specimens compared to normal adjacent tissue. Therefore, we hypothesize that 1,25(OH)2D3 regulates CYP2R1 gene expression in OSCC tumor cells. Interestingly, real-time RT-PCR analysis of total RNA isolated from OSCC cells (SCC1, SCC11B, and SCC14a) treated with 1,25(OH)2D3 showed a significant increase in CYP2R1 and vitamin D receptor (VDR) mRNA expression. Also, Western blot analysis demonstrated that 1,25(OH)2D3 treatment time-dependently increased CYP2R1 expression in these cells. 1,25(OH)2D3 stimulation of OSCC cells transiently transfected with the hCYP2R1 promoter (-2 kb)-luciferase reporter plasmid demonstrated a 4.3-fold increase in promoter activity. In addition, 1,25(OH)2D3 significantly increased c-Fos, p-c-Jun expression, and c-Jun N-terminal kinase (JNK) activity in these cells. The JNK inhibitor suppresses 1,25(OH)2D3, inducing CYP2R1 mRNA expression and gene promoter activity in OSCC cells. Furthermore, JNK inhibitor significantly decreased 1,25(OH)2D3 inhibition of OSCC tumor cell proliferation. Taken together, our results suggest that AP-1 is a downstream effector of 1,25(OH)2D3 signaling to modulate CYP2R1 gene expression in OSCC tumor cells, and vitamin D analogs could be potential therapeutic agents to control OSCC tumor progression.
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