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Vitamin D3 regulates NSUN2 expression and inhibits melanoma cell proliferation and migration

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Abstract

The activated form of vitamin D3 [1,25-dihydroxyvitamin D3; 1,25(OH)2D3] is important for various physiological processes, such as bone mineralization and calcium metabolism, and plays an anticancer role in numerous cancers as well. Its role in melanoma cells has yet to be proven. NOP2/Sun RNA methyltransferase 2 (NSUN2) is a typical RNA methyltransferase and is highly expressed in a variety of cancer cells. However, the molecular mechanisms underlying the role of 1,25(OH)2D3 and NSUN2 in melanoma cells remain largely unknown. The current study showed that 1,25(OH)2D3 could significantly and specifically inhibit the proliferation and migration of melanoma B16 cells. 1,25(OH)2D3 enhances vitamin D receptor expression while simultaneously reducing NSUN2 expression in melanoma cells. Subsequently, knockdown of NSUN2 suppressed B16 cell proliferation and migration. RNA-Seq results illuminated that DNA replication, cell proliferation and cell cycle pathways were enriched, and genes promoting these pathways were reduced after knocking down Nsun2. Dual-luciferase reporter assays showed that 1,25(OH)2D3 downregulated reporter gene expression was controlled by the Nsun2 promoter. The results suggest that 1,25(OH)2D3 binds to the vitamin D response element located upstream of the Nsun2 promoter to downregulate Nsun2 transcription activity and then affects the gene expression pattern related to cell proliferation and the cell cycle, thereby restraining B16 cell proliferation and migration.

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References

  1. None (2012) Dietary Reference Intakes for Calcium and Vitamin D [J]. Pediatrics, 130(5): e1424-e1424

  2. Chai Y et al (2021) Inhibitory effect of Astragalus Membranaceus on osteoporosis in SAMP6 mice by regulating vitaminD/FGF23/Klotho signaling pathway. Bioengineered 12(1):4464–4474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Hector, DeLuca (2004) Overview of general physiologic features and functions of vitamin D1,2,3,4. Am J Clin Nutr 80(6 Suppl):1689S–96S

    Google Scholar 

  4. Jay N, Duffy SR, Estrada DF (2022) Characterization of a Cleavable Fusion of Human CYP24A1 with Adrenodoxin reveals the variable role of Hydrophobics in Redox Partner binding. Biochemistry 61(2):57–66

    Article  CAS  PubMed  Google Scholar 

  5. Ceglia L (2008) Vitamin D and skeletal muscle tissue and function. Mol Aspects Med 29(6):407–414

    Article  CAS  PubMed  Google Scholar 

  6. Fathi N et al (2019) Role of vitamin D and vitamin D receptor (VDR) in oral cancer. Biomed Pharmacother 109:391–401

    Article  CAS  PubMed  Google Scholar 

  7. Vitamin D 3 (2021) /VDR inhibits inflammation through NF-κB pathway accompanied by resisting apoptosis and inducing autophagy in abalone Haliotis discus hannai. Cell Biol Toxicol, : 1–22

  8. Carlberg C, Velleuer E (2021) Vitamin D and the risk for cancer: a molecular analysis. Biochem Pharmacol, (3692): 114735

  9. Hsu JW et al (2011) Suppression of prostate Cancer Cell Rolling and Adhesion to Endothelium by 1α,25-Dihydroxyvitamin D3. Am J Pathol 178(2):872–880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kasiappan R et al (2012) 1,25-Dihydroxyvitamin D3 suppresses telomerase expression and human cancer growth through microRNA-498. J Biol Chem 287(49):41297–41309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chang Se et al (2015) miR-145 mediates the antiproliferative and gene regulatory effects of vitamin D3 by directly targeting E2F3 in gastric cancer cells. Oncotarget 6(10):7675–7785

    Article  PubMed  PubMed Central  Google Scholar 

  12. Liu N et al (2020) Inhibition of lung cancer by vitamin D depends on downregulation of histidine-rich calcium-binding protein. J Adv Res 29:13–22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Liu M et al (2021) 5-methylcytosine modification by Plasmodium NSUN2 stabilizes mRNA and mediates the development of gametocytes. Proc Natl Acad Sci USA 119(9):e2110713119

    Article  Google Scholar 

  14. NSUN2-mediated RNA 5-methylcytosine promotes esophageal squamous cell carcinoma progression via LIN28B-dependent GRB2 mRNA stabilization. Oncogene 40(39): 5814–5828

  15. He X et al (2022) ROR2 downregulation activates the MSX2/NSUN2/p21 regulatory axis and promotes dental pulp stem cell senescence. Stem Cells 40(3):290–302

    Article  PubMed  Google Scholar 

  16. Chen J et al (2019) M ~ 6A regulates neurogenesis and neuronal development by modulating histone methyltransferase Ezh2. Genomics Proteom Bioinf 17(2):154–168

    Article  CAS  Google Scholar 

  17. Namikawa K, Yamazaki N (2019) Targeted therapy and immunotherapy for Melanoma in Japan. Curr Treat Options Oncol 20(1):7

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kozovska Z, Gabrisova V, Kucerova L (2016) Malignant melanoma: diagnosis, treatment and cancer stem cells. Neoplasma 63(04):510–517

    Article  CAS  PubMed  Google Scholar 

  19. Alos L (2021) Molecular markers and targets in Melanoma. Cells, 10. (9):2320

  20. Tsoi J et al (2018) Multistage differentiation defines Melanoma Subtypes with Differential Vulnerability to Drug-Induced Iron-Dependent oxidative stress. Cancer Cell, : 890–904

  21. Li B et al (2019) Desferrioxamine-caffeine shows improved efficacy in chelating iron and depleting cancer stem cells. J Trace Elem Med Biology: Organ Soc Minerals Trace Elem (GMS) 52:232

    Article  Google Scholar 

  22. Kaiser CL et al (2010) 5-Ethynyl-2’-deoxyuridine labeling detects proliferating cells in the regenerating avian cochlea. Laryngoscope 119(9):1770–1775

    Article  Google Scholar 

  23. Wang Y et al (2017) STIM1 silencing inhibits the migration and invasion of A549 cells. Mol Med Rep 16(3):3283–3289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Matos DM (2020) Standardization of a compensation matrix for the use in an ISHAGE-based single-platform for CD34 + stem cell quantitation on the FACSVia flow cytometer. Int J Lab Hematol 42(2):198–205

    Article  PubMed  Google Scholar 

  25. Kern H (1986) A Rapid Bioassay to Determine Stabilities of Anticancer Agents under Conditions of the Clonogenic Assay. Vitro Cell Dev Biology 22(5):247–252

    Article  Google Scholar 

  26. Zhang C et al (2019) Downregulation of HDGF inhibits the tumorigenesis of bladder cancer cells by inactivating the PI3K-AKT signaling pathway. Cancer Manage Res 11:7909–7923

    Article  CAS  Google Scholar 

  27. J., et al., Regulation of target gene expression by the vitamin D receptor - an update on mechanisms. Reviews in Endocrine and Metabolic Disorders, (2011) 13(1): 45–55

  28. Schepelmann M, Vitamin DA (2021) Regulate the vitamin D system and cell viability in Ovarian Cancer cells. Int J Mol Sci 23(1):172

    Article  PubMed  PubMed Central  Google Scholar 

  29. Prentice A, Vitamin (2013) D deficiency: a global perspective. Nutr Rev 66(10 Suppl 2):S153–S164

    Google Scholar 

  30. Guan H et al (2013) 1,25-Dihydroxyvitamin D3 upregulates expression of hsa-let-7a-2 through the interaction of VDR/VDRE in human lung cancer A549 cells. Gene 522(2):142–146

    Article  CAS  PubMed  Google Scholar 

  31. Wang W, Welsh JE, Tenniswood M (2013) 1,25-Dihydroxyvitamin D3 modulates lipid metabolism in prostate cancer cells through miRNA mediated regulation of PPARA. J Steroid Biochem Mol Biol 136:47–251

    Article  Google Scholar 

  32. Xiaoyu et al (2016) RNA methyltransferase NSUN2 promotes stress-induced HUVEC senescence. Oncotarget 7(15):19099–19110

    Article  Google Scholar 

  33. Barbieri I, Kouzarides T (2020) Role of RNA modifications in cancer. Nat Rev Cancer 20(6):303–322

    Article  CAS  PubMed  Google Scholar 

  34. Wang X et al (2009) MicroRNAs181 regulate the expression of p27Kip1 in human myeloid leukemia cells induced to differentiate by 1,25-dihydroxyvitamin D3. Cell Cycle 8(5):736–741

    Article  CAS  PubMed  Google Scholar 

  35. Chang Se et al (2015) miR-145 mediates the antiproliferative and gene regulatory effects of vitamin D3 by directly targeting E2F3 in gastric cancer cells. Oncotarget 6(10):7675–7685

    Article  PubMed  PubMed Central  Google Scholar 

  36. Ting HJ et al (2013) Identification of microRNA-98 as a therapeutic target inhibiting prostate Cancer growth and a Biomarker Induced by vitamin D. J Biol Chem 288(1):1–9

    Article  CAS  PubMed  Google Scholar 

  37. Hao T et al (2015) NSun2 delays replicative senescence by repressing p27 (KIP1) translation and elevating CDK1 translation. Aging 7(12):1143–1155

    Article  Google Scholar 

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Authors and Affiliations

  1. School of Biological Science and Engineering, Shaanxi University of Technology, Dongguan Street South Campus, Hanzhong, 723001, Shaanxi Province, China

    Ling Wang, Qiang Zhang, Jinping Wang, Hongzhao Lu, Wenxian Zeng & Tao Zhang

  2. College of Life Sciences, Key Laboratory of Plant Secondary Metabolism and Regulation of Zhejiang Province, Zhejiang Sci-Tech University, Hangzhou, 310018, China

    Qiang Zhang

  3. QinLing-Bashan Mountains Bioresources Comprehensive Development C. I. C, Shaanxi University of Technology, Hanzhong, 723001, China

    Wenxian Zeng & Tao Zhang

  4. Qinba State Key Laboratory of Biological Resources and Ecological Environment, Shaanxi University of Technology, Hanzhong, 723001, China

    Wenxian Zeng

  5. Shaanxi Province Key Laboratory of Bioresources, Shaanxi University of Technology, Hanzhong, 723001, China

    Tao Zhang

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  1. Ling Wang
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  2. Qiang Zhang
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  3. Jinping Wang
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  4. Hongzhao Lu
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Contributions

LW contributed to data collection and analyzing and manuscript writing. QZ contributed to cell culture and manuscript writing. JPW and HZL contributed to data analysis.  WXZ contributed to conceptualization and methodology. TZ contributed to project administration and supervision. All authors reviewed the manuscript.

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Correspondence to Tao Zhang.

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Ling Wang and Qiang Zhang have contributed equally to this work and share first authorship.

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Wang, L., Zhang, Q., Wang, J. et al. Vitamin D3 regulates NSUN2 expression and inhibits melanoma cell proliferation and migration. Mol Divers (2023). https://doi.org/10.1007/s11030-023-10720-9

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  • DOI: https://doi.org/10.1007/s11030-023-10720-9

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