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

Zhang,Yang-Jie; Xie,Ran; Jiang,Jie; Zhai,Li; Yang,Cong-Hui; Zhang,Jing; Wang,Xi; Chen,Dong-Xue; Niu,Hua-Tao; Chen,Long

doi:10.3892/or.2022.8334

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
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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
Published online on: May 19, 2022 https://doi.org/10.3892/or.2022.8334
Article Number: 123
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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