5AzadC suppresses melanoma progression by inhibiting GAS5 hypermethylation.
Oncol Rep
; 48(1)2022 07.
Article
de En
| MEDLINE
| ID: mdl-35593315
ABSTRACT
The indepth 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 arrestspecific 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 methylationspecific 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 5Aza2'deoxycytidine (5AzadC), GAS5 methylation was significantly reversed. The analysis of melanoma cell proliferation revealed that 5AzadC inhibited A375 and SKMEL110 cell proliferation in a timedependent manner. Further analysis of apoptosis demonstrated that 5AzadC significantly increased the apoptosis level of the two cell lines. Moreover, migration analysis of melanoma cells revealed that 5AzadC significantly reduced cell migration. Furthermore, 5AzadC significantly decreased the invasive ability of the two cell lines. However, when the expression of GAS5 was silenced, the effects of 5AzadC 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 5AzadC, the volume and weight of xenograft tumors and Ki67 expression were significantly reduced, and caspase3 activity and GAS5 expression were enhanced; following the silencing of GAS5, the antitumor effect of 5AzadC was significantly blocked. On the whole, the present study demonstrates that 5AzadC inhibits the growth of melanoma, and its function may be related to the methylation modification of GAS5.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
ARN long non codant
/
Mélanome
Limites:
Animals
/
Humans
Langue:
En
Journal:
Oncol Rep
Sujet du journal:
NEOPLASIAS
Année:
2022
Type de document:
Article