ArticleThe Journal of biological chemistry2012
1,25-Dihydroxyvitamin D3 suppresses telomerase expression and human cancer growth through microRNA-498.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
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Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 123 citations in OpenAlex.
- Vitamin D and Ovarian Cancer: Systematic Review of the Literature with a Focus on Molecular Mechanisms.Cells · 2020Pooled it
- Vitamin D-Related Signaling and Epigenetic Regulation: Evidence from Experimental, Observational, and Interventional Studies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Nutriepigenetics and nutriepigenomics: Exploring the interactions between nutrition, epigenetics, and epigenomics in the pathogenesis of noncommunicable diseases.Genetics and molecular biology · 2026Article
- Role of microRNA-498 and microRNA-410 in neonatal hypoxic-ischemic encephalopathy.Clinical and experimental pediatrics · 2025Article
- Nutri-Epigenetic Regulation of Vitamin D-Impact on Metabolism and Biological Functions: Narrative Review.Metabolites · 2025Review
- Vitamin D3 regulates NSUN2 expression and inhibits melanoma cell proliferation and migration.Molecular diversity · 2024Article
- Telomerase Inhibition in the Treatment of Leukemia: A Comprehensive Review.Antioxidants (Basel, Switzerland) · 2024Review
- Systematic vitamin D supplementation is associated with improved outcomes and reduced thyroid adverse events in patients with cancer treated with immune checkpoint inhibitors: results from the prospective PROVIDENCE study.Cancer immunology, immunotherapy : CII · 2023Observational
- Combining old and new concepts in targeting telomerase for cancer therapy: transient, immediate, complete and combinatory attack (TICCA).Cancer cell international · 2023Review
- Role of Vitamin D in Head and Neck Cancer-Immune Function, Anti-Tumour Effect, and Its Impact on Patient Prognosis.Nutrients · 2023Review
- Vitamin D, a Regulator of Androgen Levels, Is Not Correlated to PSA Serum Levels in a Cohort of the Middle Italy Region Participating to a Prostate Cancer Screening Campaign.Journal of clinical medicine · 2023Article
- miRNA deregulation and relationship with metabolic parameters after Mediterranean dietary intervention in BRCA-mutated women.Frontiers in oncology · 2023Article
- The Effect of Vitamin D and Its Analogs in Ovarian Cancer.Nutrients · 2022Review
- Review
- Long non-coding RNA (lncRNA) HOXB-AS3 promotes cell proliferation and inhibits apoptosis by regulating ADAM9 expression through targeting miR-498-5p in endometrial carcinoma.The Journal of international medical research · 2021Article
- Vitamin D modulation and microRNAs in gastric cancer: prognostic and therapeutic role.Translational cancer research · 2021Review
- Telomerase Regulation: A Role for Epigenetics.Cancers · 2021Review
- Article
- Association among Vitamin D, Retinoic Acid-Related Orphan Receptors, and Vitamin D Hydroxyderivatives in Ovarian Cancer.Nutrients · 2020Article
- Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Telomerase is an essential enzyme that counteracts the telomere attrition accompanying DNA replication during cell division. Regulation of the promoter activity of the gene encoding its catalytic subunit, the telomerase reverse transcriptase, is established as the dominant mechanism conferring the high telomerase activity in proliferating cells, such as embryonic stem and cancer cells. This study reveals a new mechanism of telomerase regulation through non-coding small RNA by showing that microRNA-498 (miR-498) induced by 1,25-dihydroxyvitamin D3 (1,25(OH)(2)D(3)) decreases the mRNA expression of the human telomerase reverse transcriptase. MiR-498 was first identified in a microarray analysis as the most induced microRNA by 1,25(OH)(2)D(3) in ovarian cancer cells and subsequently validated by quantitative polymerase chain reaction assays in multiple human cancer types. A functional vitamin D response element was defined in the 5-prime regulatory region of the miR-498 genome, which is occupied by the vitamin D receptor and its coactivators. Further studies showed that miR-498 targeted the 3-prime untranslated region of human telomerase reverse transcriptase mRNA and decreased its expression. The levels of miR-498 expression were decreased in malignant human ovarian tumors as well as human ovarian cancer cell lines. The ability of 1,25(OH)(2)D(3) to decrease human telomerase reverse transcriptase mRNA and to suppress ovarian cancer growth was compromised when miR-498 was depleted using the sponges in cell lines and mouse tumor models. Taken together, our studies define a novel mechanism of telomerase regulation by small non-coding RNAs and identify miR-498 as an important mediator for the anti-tumor activity of 1,25(OH)(2)D(3).
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Registered trials
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