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5‑Aza‑dC suppresses melanoma progression by inhibiting GAS5 hypermethylation

  • Authors:
    • Yang-Jie Zhang
    • Ran Xie
    • Jie Jiang
    • Li Zhai
    • Cong-Hui Yang
    • Jing Zhang
    • Xi Wang
    • Dong-Xue Chen
    • Hua-Tao Niu
    • Long Chen
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedics (Spine Special), Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province, Kunming, Yunnan 650118, P.R. China, Department of PET/CT Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province, Kunming, Yunnan 650118, P.R. China, Department of Laboratory Testing, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province, Kunming, Yunnan 650118, P.R. China, Department of Dentistry, Hospital of Traditional Chinese and Western Medicine, Kunming, Yunnan 650224, P.R. China, Department of Pharmacy, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650118, P.R. China, Department of Neurological Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650118, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 123
    |
    Published online on: May 19, 2022
       https://doi.org/10.3892/or.2022.8334
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Abstract

The in‑depth study of melanoma pathogenesis has revealed that epigenetic modifications, particularly DNA methylation, is a universal inherent feature of the development and progression of melanoma. In the present study, the analysis of the tumor suppressor gene growth arrest‑specific transcript 5 (GAS5) demonstrated that its expression was downregulated in melanoma, and its expression level had a certain negative association with its methylation modification level. The promoter of GAS5 presented with detectable CpG islands, and methylation‑specific polymerase chain reaction analysis demonstrated that GAS5 was actually modified by methylation in melanoma tissues and cells; however, no methylation modification of GAS5 was detected in normal tissues. Following the treatment of melanoma cells with 5‑Aza‑2'‑deoxycytidine (5‑Aza‑dC), GAS5 methylation was significantly reversed. The analysis of melanoma cell proliferation revealed that 5‑Aza‑dC inhibited A375 and SK‑MEL‑110 cell proliferation in a time‑dependent manner. Further analysis of apoptosis demonstrated that 5‑Aza‑dC significantly increased the apoptosis level of the two cell lines. Moreover, migration analysis of melanoma cells revealed that 5‑Aza‑dC significantly reduced cell migration. Furthermore, 5‑Aza‑dC significantly decreased the invasive ability of the two cell lines. However, when the expression of GAS5 was silenced, the effects of 5‑Aza‑dC on cell proliferation, apoptosis, invasion and migration were not significant. Furthermore, the subcutaneous injection of A375 cells in nude mice successfully resulted in xenograft tumor formation. However, following an intraperitoneal injection of 5‑Aza‑dC, the volume and weight of xenograft tumors and Ki‑67 expression were significantly reduced, and caspase‑3 activity and GAS5 expression were enhanced; following the silencing of GAS5, the antitumor effect of 5‑Aza‑dC was significantly blocked. On the whole, the present study demonstrates that 5‑Aza‑dC inhibits the growth of melanoma, and its function may be related to the methylation modification of GAS5.
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View References

1 

Elder DE: Melanoma progression. Pathology. 48:147–154. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Krathen M: Malignant melanoma: Advances in diagnosis, prognosis, and treatment. Semin Cutan Med Surg. 31:45–49. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Micevic G, Theodosakis N and Bosenberg M: Aberrant DNA methylation in melanoma: Biomarker and therapeutic opportunities. Clin Epigenetics. 9:342017. View Article : Google Scholar : PubMed/NCBI

4 

Guo W, Zhu L, Zhu R, Chen Q, Wang Q and Chen JQ: A four-DNA methylation biomarker is a superior predictor of survival of patients with cutaneous melanoma. Elife. 8:e443102019. View Article : Google Scholar : PubMed/NCBI

5 

Tanemura A, Terando AM, Sim MS, van Hoesel AQ, de Maat MF, Morton DL and Hoon DS: CpG island methylator phenotype predicts progression of malignant melanoma. Clin Cancer Res. 15:1801–1807. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Bhan A, Soleimani M and Mandal SS: Long noncoding RNA and cancer: A new paradigm. Cancer Res. 77:3965–3981. 2017. View Article : Google Scholar : PubMed/NCBI

7 

Yang X, Xie Z, Lei X and Gan R: Long non-coding RNA GAS5 in human cancer. Oncol Lett. 20:2587–2594. 2020. View Article : Google Scholar

8 

Chen L, Yang H, Xiao Y, Tang X, Li Y, Han Q, Fu J, Yang Y and Zhu Y: LncRNA GAS5 is a critical regulator of metastasis phenotype of melanoma cells and inhibits tumor growth in vivo. Onco Targets Ther. 9:4075–4087. 2016. View Article : Google Scholar : PubMed/NCBI

9 

Ma X, Yu L, Wang P and Yang X: Discovering DNA methylation patterns for long non-coding RNAs associated with cancer subtypes. Comput Biol Chem. 69:164–170. 2017. View Article : Google Scholar : PubMed/NCBI

10 

Cheng M, Sun L, Huang K, Yue X, Chen J, Zhang Z, Zhao B and Bian E: A signature of nine lncRNA methylated genes predicts survival in patients with glioma. Front Oncol. 11:6464092021. View Article : Google Scholar

11 

Linnekamp JF, Butter R, Spijker R, Medema JP and van Laarhoven HWM: Clinical and biological effects of demethylating agents on solid tumours-a systematic review. Cancer Treat Rev. 54:10–23. 2017. View Article : Google Scholar : PubMed/NCBI

12 

Momparler RL: Epigenetic therapy of cancer with 5-aza-2′-deoxycytidine (decitabine). Semin Oncol. 32:443–451. 2005. View Article : Google Scholar

13 

Rajaii F, Asnaghi L, Enke R, Merbs SL, Handa JT and Eberhart CG: The demethylating agent 5-Aza reduces the growth, invasiveness, and clonogenicity of uveal and cutaneous melanoma. Invest Ophthalmol Vis Sci. 55:6178–6186. 2014. View Article : Google Scholar

14 

Lindner DJ, Wu Y, Haney R, Jacobs BS, Fruehauf JP, Tuthill R and Borden EC: Thrombospondin-1 expression in melanoma is blocked by methylation and targeted reversal by 5-Aza-deoxycytidine suppresses angiogenesis. Matrix Biol. 32:123–132. 2013. View Article : Google Scholar

15 

Wang W, Wang J, Li M, Ying J and Jing H: 5-Azacitidine induces demethylation of PTPL1 and inhibits growth in non-Hodgkin lymphoma. Int J Mol Med. 36:698–704. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

17 

Numoto K, Yoshida A, Sugihara S, Kunisada T, Morimoto Y, Yoneda Y, Fujita Y, Nishida K, Ouchida M and Ozaki T: Frequent methylation of RASSF1A in synovial sarcoma and the anti-tumor effects of 5-aza-2′-deoxycytidine against synovial sarcoma cell lines. J Cancer Res Clin Oncol. 136:17–25. 2010. View Article : Google Scholar

18 

Chen L, Yang H, Yi Z, Jiang L, Li Y, Han Q, Yang Y, Zhang Q, Yang Z, Kuang Y and Zhu Y: LncRNA GAS5 regulates redox balance and dysregulates the cell cycle and apoptosis in malignant melanoma cells. J Cancer Res Clin Oncol. 145:637–652. 2019. View Article : Google Scholar

19 

Bian D, Shi W, Shao Y, Li P and Song G: Long non-coding RNA GAS5 inhibits tumorigenesis via miR-137 in melanoma. Am J Transl Res. 9:1509–1520. 2017.PubMed/NCBI

20 

Qi Y, Cui Q, Zhang W, Yao R, Xu D and Zhang F: Long non-coding RNA GAS5 targeting microRNA-21 to suppress the invasion and epithelial-mesenchymal transition of uveal melanoma. Cancer Manag Res. 12:12259–12267. 2020. View Article : Google Scholar : PubMed/NCBI

21 

Xu W, Yan Z, Hu F, Wei W, Yang C and Sun Z: Long non-coding RNA GAS5 accelerates oxidative stress in melanoma cells by rescuing EZH2-mediated CDKN1C downregulation. Cancer Cell Int. 20:1162020. View Article : Google Scholar

22 

Moore LD, Le T and Fan G: DNA methylation and its basic function. Neuropsychopharmacology. 38:23–38. 2013. View Article : Google Scholar : PubMed/NCBI

23 

Kulis M and Esteller M: DNA methylation and cancer. Adv Genet. 70:27–56. 2010. View Article : Google Scholar

24 

Li J, Li L, Yuan H, Huang XW, Xiang T and Dai S: Up-regulated lncRNA GAS5 promotes chemosensitivity and apoptosis of triple-negative breast cancer cells. Cell Cycle. 18:1965–1975. 2019. View Article : Google Scholar : PubMed/NCBI

25 

Yang W, Xu X, Hong L, Wang Q, Huang J and Jiang L: Upregulation of lncRNA GAS5 inhibits the growth and metastasis of cervical cancer cells. J Cell Physiol. 234:23571–23580. 2019. View Article : Google Scholar

26 

Wang Y, Xin S, Zhang K, Shi R and Bao X: Low GAS5 levels as a predictor of poor survival in patients with lower-grade gliomas. J Oncol. 2019:17850422019. View Article : Google Scholar

27 

Wang K, Li J, Xiong G, He G, Guan X, Yang K and Bai Y: Negative regulation of lncRNA GAS5 by miR-196a inhibits esophageal squamous cell carcinoma growth. Biochem Biophys Res Commun. 495:1151–1157. 2018. View Article : Google Scholar : PubMed/NCBI

28 

Budden T, van der Westhuizen A and Bowden NA: Sequential decitabine and carboplatin treatment increases the DNA repair protein XPC, increases apoptosis and decreases proliferation in melanoma. BMC Cancer. 18:1002018. View Article : Google Scholar : PubMed/NCBI

29 

Tawbi HA, Beumer JH, Tarhini AA, Moschos S, Buch SC, Egorin MJ, Lin Y, Christner S and Kirkwood JM: Safety and efficacy of decitabine in combination with temozolomide in metastatic melanoma: A phase I/II study and pharmacokinetic analysis. Ann Oncol. 24:1112–1119. 2013. View Article : Google Scholar

30 

van der Westhuizen A, Knoblauch N, Graves MC, Levy R, Vilain RE and Bowden NA: Pilot early phase II study of decitabine and carboplatin in patients with advanced melanoma. Medicine (Baltimore). 99:e207052020. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zhang Y, Xie R, Jiang J, Zhai L, Yang C, Zhang J, Wang X, Chen D, Niu H, Chen L, Chen L, et al: 5‑Aza‑dC suppresses melanoma progression by inhibiting GAS5 hypermethylation. Oncol Rep 48: 123, 2022.
APA
Zhang, Y., Xie, R., Jiang, J., Zhai, L., Yang, C., Zhang, J. ... Chen, L. (2022). 5‑Aza‑dC suppresses melanoma progression by inhibiting GAS5 hypermethylation. Oncology Reports, 48, 123. https://doi.org/10.3892/or.2022.8334
MLA
Zhang, Y., Xie, R., Jiang, J., Zhai, L., Yang, C., Zhang, J., Wang, X., Chen, D., Niu, H., Chen, L."5‑Aza‑dC suppresses melanoma progression by inhibiting GAS5 hypermethylation". Oncology Reports 48.1 (2022): 123.
Chicago
Zhang, Y., Xie, R., Jiang, J., Zhai, L., Yang, C., Zhang, J., Wang, X., Chen, D., Niu, H., Chen, L."5‑Aza‑dC suppresses melanoma progression by inhibiting GAS5 hypermethylation". Oncology Reports 48, no. 1 (2022): 123. https://doi.org/10.3892/or.2022.8334
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang Y, Xie R, Jiang J, Zhai L, Yang C, Zhang J, Wang X, Chen D, Niu H, Chen L, Chen L, et al: 5‑Aza‑dC suppresses melanoma progression by inhibiting GAS5 hypermethylation. Oncol Rep 48: 123, 2022.
APA
Zhang, Y., Xie, R., Jiang, J., Zhai, L., Yang, C., Zhang, J. ... Chen, L. (2022). 5‑Aza‑dC suppresses melanoma progression by inhibiting GAS5 hypermethylation. Oncology Reports, 48, 123. https://doi.org/10.3892/or.2022.8334
MLA
Zhang, Y., Xie, R., Jiang, J., Zhai, L., Yang, C., Zhang, J., Wang, X., Chen, D., Niu, H., Chen, L."5‑Aza‑dC suppresses melanoma progression by inhibiting GAS5 hypermethylation". Oncology Reports 48.1 (2022): 123.
Chicago
Zhang, Y., Xie, R., Jiang, J., Zhai, L., Yang, C., Zhang, J., Wang, X., Chen, D., Niu, H., Chen, L."5‑Aza‑dC suppresses melanoma progression by inhibiting GAS5 hypermethylation". Oncology Reports 48, no. 1 (2022): 123. https://doi.org/10.3892/or.2022.8334
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