Genetic Markers Indicate that 1,25-dihydroxyvitaminD Treatment may not Protect Against HepatocellularCarcinoma

ÇOLAK, Ertuğrul; ÖNER, Çağrı

doi:10.14744/ejmo.2021.65874

Genetic Markers Indicate that 1,25-dihydroxyvitaminD Treatment may not Protect Against HepatocellularCarcinoma

Çağrı ÖNER, (Maltepe Üniversitesi, Tıp Fakültesi, Tıbbi Biyoloji ve Genetik Anabilim Dalı, İstanbul, Türkiye)

Ertuğrul ÇOLAK (Eskişehir Osmangazi Üniversitesi, Tıp Fakültesi, Biyoistatistik Anabilim Dalı, Eskişehir, Türkiye)

Eurasian Journal of Medicine and Oncology

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Yıl: 2021 Cilt: 5 Sayı: 2 Sayfa Aralığı: 117 - 122 Metin Dili: İngilizce DOI: 10.14744/ejmo.2021.65874 İndeks Tarihi: 06-02-2022

Genetic Markers Indicate that 1,25-dihydroxyvitaminD Treatment may not Protect Against HepatocellularCarcinoma

Öz:

Objectives: The impact of 1,25-dihydroxyvitamin D on hepatocellular carcinoma (HCC) cells is a complicated area. Inthis study, we aimed to clarify the effect of 1,25-dihydroxyvitamin D on HCC cells according to genetic markers. Methods: The optimal concentration of 1,25-dihydroxyvitamin D is treated to HepG2 cells (250 nM at the 48th hour).From treated HepG2 cells, total Ribonucleic Acid (RNA) was isolated, and Ki-67, MMP-2, MMP-9, HIF-1α, hTERT, and piR 823 gene expressions were determined by SYBR Green-based real-time polymerase chain reaction. Results: : Increased expressions of Ki-67, hTERT, and piR-823 were determined compared with the control group at the48th hour after treatment (p<0.001), while decreased gene expressions of MMP-2, MMP-9, and HIF-1α were observedcompared with the control group (p<0.001). Conclusion: Currently, there are several different opinions about the usage of vitamin D, especially in HCC. In addi tion to researchers who argue that vitamin D has anticarcinogenic and protective properties, an increasing numberof researchers argue that tumor cells can become aggressive after HCC occurs. According to our results, it was deter mined that vitamin D causes HepG2 HCC cells to become aggressive in terms of gene expression in the parametersused as a marker for proliferation, adhesion, and differentiation.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Manson JE, Mayne ST, Clinton SK. Vitamin D and prevention of cancer--ready for prime time? N Engl J Med 2011;364:1385–7.
2. Farhan M, Rizvi A, Naseem I, Hadi SM, Ahmad A. Targeting increased copper levels in diethylnitrosamine induced hepatocellular carcinoma cells in rats by epigallocatechin-3-gallate. Tumour Biol 2015;36:8861–7.
3. Chiang KC, Yeh CN, Chen MF, Chen TC. Hepatocellular carcinoma and vitamin D: a review. J Gastroenterol Hepatol 2011;26:1597–603.
4. McGlynn KA, London WT. The global epidemiology of hepatocellular carcinoma: present and future. Clin Liver Dis 2011;15:223–43, vii–x.
5. Mahmoud AM, El-Shemy HA. Cytotoxic profiling of some compounds of natural origin against HepG2 liver cancer cell line in-vitro. J Arid Land 2012;22:191–4.
6. Glowka E, Stasiak J, Lulek J. Drug delivery systems for vitamin D supplementation and therapy. Pharmaceutics 2019;11:347.
7. Pivonello C, Provvisiero DP, Negri M, Di GG, De AC, Galdiero G. Potential role of vitamin D in restoring sensitivity to mTOR inhibitors in hepatocellular carcinoma (HCC): 1,25(OH)vitamin D (VITD) reverts everolimus (EVE) resistance in a HCC cell line. Endocrine Abstracts 2016;41.
8. Pourgholami MH, Akhter J, Lu Y, Morris DL. In vitro and in vivo inhibition of liver cancer cells by 1,25-dihydroxyvitamin D3. Cancer Lett 2000;151:97-102.
9. Fingas CD, Altinbas A, Schlattjan M, Beilfuss A, Sowa JP, Sydor S, et al. Expression of apoptosis- and vitamin D pathway-related genes in hepatocellular carcinoma. Digestion 2013;87:176–81.
10. Huang J, Yang G, Huang Y, Kong W, Zhang S. 1,25(OH)2D3 inhibits the progression of hepatocellular carcinoma via downregulating HDAC2 and upregulating P21(WAFI/CIP1). Mol Med Rep 2016;13:1373–80.
11. Huang J, Yang G, Huang Y, Zhang S. 1,25(OH)2D3 induced apoptosis of human hepatocellular carcinoma cells in vitro and inhibited their growth in a nude mouse xenograft model by regulating histone deacetylase 2. Biochimie 2018;146:28– 34.
12. Schmitt-Graff A, Ertelt V, Allgaier HP, Koelble K, Olschewski M, Nitschke R, et al. Cellular retinol-binding protein-1 in hepatocellular carcinoma correlates with beta-catenin, Ki-67 index, and patient survival. Hepatology 2003;38:470–80.
13. Zhang JG, Zhou HM, Zhang X, Mu W, Hu JN, Liu GL, et al. Hypoxic induction of vasculogenic mimicry in hepatocellular carcinoma: role of HIF-1 alpha, RhoA/ROCK and Rac1/PAK signaling. BMC cancer 2020;20:32.
14. Lin XL, Li K, Yang Z, Chen B, Zhang T. Dulcitol suppresses proliferation and migration of hepatocellular carcinoma via regulating SIRT1/p53 pathway. Phytomedicine 2020;66:153112.
15. Huang S, Van Arsdall M, Tedjarati S, McCarty M, Wu W, Langley R, et al. Contributions of stromal metalloproteinase-9 to angiogenesis and growth of human ovarian carcinoma in mice. JNCI 2002;94:1134–42.
16. Choi SH, Cho KJ, Yun SH, Jin B, Lee HY, Ro SW, et al. HKR3 regulates cell cycle through the inhibition of hTERT in hepatocellular carcinoma cell lines. J Cancer 2020;11:2442–52.
17. Öner Ç. Two different mechanisms of two different non-coding RNAs—MicroRNAs and PIWI-interacting RNAs: From origin to cancer. In: Mallick B, editor. AGO-Driven Non-Coding RNAs. 1st ed. Cambridge, Massachusetts: Elsevier; 2019. p. 3–34.
18. Öner Ç, İsan H, Aktaş RG, Çolak E. The effect of Vitamin D on hepatocellular carcinoma. Osmangazi Journal of Medicine 2020;42:301–10.
19. Mankgopo MK, Hairwadzi H. Role of vitamin D levels in viral infections and possible epigenetic alterations. Cellular Immunology & Immunotherapeutics 2016;1:1–6.
20. Haussler MR, Whitfield GK, Haussler CA, Hsieh JC, Thompson PD, Selznick SH, et al. The nuclear vitamin D receptor: biological and molecular regulatory properties revealed. J Bone Miner Res 1998;13:325–49.
21. Umesono K, Murakami KK, Thompson CC, Evans RM. Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors. Cell 1991;65:1255–66.
22. Jenkins K. Vitamin D does not prevent cancer: Study. Medscape Medical News; 2018. Available at: https://www.med-scape.com/viewarticle/899716#:~:text=Conflicting%20Results,lung%20cancer%2C%20even%20in%20nonsmokers. Accessed May 26, 2021.
23. Scragg R, Khaw KT, Toop L, Sluyter J, Lawes CMM, Waayer D, et al. Monthly high-dose vitamin D supplementation and cancer risk: a post hoc analysis of the vitamin D assessment randomized clinical trial. JAMA Oncol 2018;4:e182178.
24. Lappe J, Watson P, Travers-Gustafson D, Recker R, Garland C, Gorham E, et al. Effect of vitamin D and calcium supplementation on cancer incidence in older women: a randomized clinical trial. JAMA 2017;317:1234-43.
25. Ben-Shoshan M, Amir S, Dang DT, Dang LH, Weisman Y, Mabjeesh NJ. 1alpha,25-dihydroxyvitamin D3 (Calcitriol) inhibits hypoxia-inducible factor-1/vascular endothelial growth factor pathway in human cancer cells. Mol Cancer Ther 2007;6:1433– 9.
26. Kim SH, Baek MS, Yoon DS, Park JS, Yoon BW, Oh BS, et al. Vitamin D inhibits expression and activity of matrix metalloproteinase in human lung fibroblasts (HFL-1) cells. Tuberc Respir Dis (Seoul) 2014;77:73–80.
27. Kang SN, Kim SH, Chung SW, Lee MH, Kim HJ, Kim TS. Enhancement of 1 alpha,25-dihydroxyvitamin D(3)-induced differentiation of human leukaemia HL-60 cells into monocytes by parthenolide via inhibition of NF-kappa B activity. Br J Pharmacol 2002;135:1235–44.
28. Zarei M, Zarezadeh M, Hamedi Kalajahi F, Javanbakht MH. The relationship between vitamin D and telomere/telomerase: a comprehensive review. J Frailty Aging 2021;10:2–9
29. Sobecki M, Mrouj K, Colinge J, Gerbe F, Jay P, Krasinska L, et al. Cell-cycle regulation accounts for variability in Ki-67 expression levels. Cancer Res 2017;77:2722–34.
30. Endl E, Gerdes J. The Ki-67 protein: fascinating forms and an unknown function. Exp Cell Res 2000;257:231–7.
31. Liu X, Wang Y, Chang G, Wang F, Wang F, Geng X. Alternative splicing of hTERT Pre-mRNA: a potential strategy for the regulation of telomerase activity. Int J Mol Sci 2017;18:567.
32. Zhang Y, Toh L, Lau P, Wang X. Human telomerase reverse transcriptase (hTERT) is a novel target of the Wnt/β-catenin pathway in human cancer. J Biol Chem 2012;287:32494–511.
33. Leao R, Apolonio JD, Lee D, Figueiredo A, Tabori U, Castelo-Branco P. Mechanisms of human telomerase reverse transcriptase (hTERT) regulation: clinical impacts in cancer. J Biomed Sci 2018;25:22.
34. Xiao Z, Shen J, Zhang L, Li M, Hu W, Cho C. Therapeutic targeting of noncoding RNAs in hepatocellular carcinoma: Recent progress and future prospects. Oncol Lett 2018;15:3395–402.
35. Zhu H, Wang X, Shi H, Su S, Harshfield GA, Gutin B, et al. A genome-wide methylation study of severe vitamin D deficiency in African American adolescents. J Pediatr 2013;162:1004–9. e1.
36. Yin J, Jiang XY, Qi W, Ji CG, Xie XL, Zhang DX, et al. piR-823 contributes to colorectal tumorigenesis by enhancing the transcriptional activity of HSF1. Cancer Sci 2017;108:1746–56.
37. Cui L, Lou Y, Zhang X, Zhou H, Deng H, Song H, et al. Detection of circulating tumor cells in peripheral blood from patients with gastric cancer using piRNAs as markers. Clin Biochem 2011;44:1050–7.
38. Cheng J, Deng H, Xiao B, Zhou H, Zhou F, Shen Z, et al. piR-823, a novel non-coding small RNA, demonstrates in vitro and in vivo tumor suppressive activity in human gastric cancer cells. Cancer Lett 2012;315:12–7.
39. Yan H, Wu QL, Sun CY, Ai LS, Deng J, Zhang L, et al. piRNA-823 contributes to tumorigenesis by regulating de novo DNA methylation and angiogenesis in multiple myeloma. Leukemia 2015;29:196–206.

APA	ÖNER Ç, ÇOLAK E (2021). Genetic Markers Indicate that 1,25-dihydroxyvitaminD Treatment may not Protect Against HepatocellularCarcinoma. , 117 - 122. 10.14744/ejmo.2021.65874
Chicago	ÖNER Çağrı,ÇOLAK Ertuğrul Genetic Markers Indicate that 1,25-dihydroxyvitaminD Treatment may not Protect Against HepatocellularCarcinoma. (2021): 117 - 122. 10.14744/ejmo.2021.65874
MLA	ÖNER Çağrı,ÇOLAK Ertuğrul Genetic Markers Indicate that 1,25-dihydroxyvitaminD Treatment may not Protect Against HepatocellularCarcinoma. , 2021, ss.117 - 122. 10.14744/ejmo.2021.65874
AMA	ÖNER Ç,ÇOLAK E Genetic Markers Indicate that 1,25-dihydroxyvitaminD Treatment may not Protect Against HepatocellularCarcinoma. . 2021; 117 - 122. 10.14744/ejmo.2021.65874
Vancouver	ÖNER Ç,ÇOLAK E Genetic Markers Indicate that 1,25-dihydroxyvitaminD Treatment may not Protect Against HepatocellularCarcinoma. . 2021; 117 - 122. 10.14744/ejmo.2021.65874
IEEE	ÖNER Ç,ÇOLAK E "Genetic Markers Indicate that 1,25-dihydroxyvitaminD Treatment may not Protect Against HepatocellularCarcinoma." , ss.117 - 122, 2021. 10.14744/ejmo.2021.65874
ISNAD	ÖNER, Çağrı - ÇOLAK, Ertuğrul. "Genetic Markers Indicate that 1,25-dihydroxyvitaminD Treatment may not Protect Against HepatocellularCarcinoma". (2021), 117-122. https://doi.org/10.14744/ejmo.2021.65874

APA	ÖNER Ç, ÇOLAK E (2021). Genetic Markers Indicate that 1,25-dihydroxyvitaminD Treatment may not Protect Against HepatocellularCarcinoma. Eurasian Journal of Medicine and Oncology, 5(2), 117 - 122. 10.14744/ejmo.2021.65874
Chicago	ÖNER Çağrı,ÇOLAK Ertuğrul Genetic Markers Indicate that 1,25-dihydroxyvitaminD Treatment may not Protect Against HepatocellularCarcinoma. Eurasian Journal of Medicine and Oncology 5, no.2 (2021): 117 - 122. 10.14744/ejmo.2021.65874
MLA	ÖNER Çağrı,ÇOLAK Ertuğrul Genetic Markers Indicate that 1,25-dihydroxyvitaminD Treatment may not Protect Against HepatocellularCarcinoma. Eurasian Journal of Medicine and Oncology, vol.5, no.2, 2021, ss.117 - 122. 10.14744/ejmo.2021.65874
AMA	ÖNER Ç,ÇOLAK E Genetic Markers Indicate that 1,25-dihydroxyvitaminD Treatment may not Protect Against HepatocellularCarcinoma. Eurasian Journal of Medicine and Oncology. 2021; 5(2): 117 - 122. 10.14744/ejmo.2021.65874
Vancouver	ÖNER Ç,ÇOLAK E Genetic Markers Indicate that 1,25-dihydroxyvitaminD Treatment may not Protect Against HepatocellularCarcinoma. Eurasian Journal of Medicine and Oncology. 2021; 5(2): 117 - 122. 10.14744/ejmo.2021.65874
IEEE	ÖNER Ç,ÇOLAK E "Genetic Markers Indicate that 1,25-dihydroxyvitaminD Treatment may not Protect Against HepatocellularCarcinoma." Eurasian Journal of Medicine and Oncology, 5, ss.117 - 122, 2021. 10.14744/ejmo.2021.65874
ISNAD	ÖNER, Çağrı - ÇOLAK, Ertuğrul. "Genetic Markers Indicate that 1,25-dihydroxyvitaminD Treatment may not Protect Against HepatocellularCarcinoma". Eurasian Journal of Medicine and Oncology 5/2 (2021), 117-122. https://doi.org/10.14744/ejmo.2021.65874