MATN4 as a target gene of HIF-1α promotes the proliferation and metastasis of osteosarcoma.
Aging (Albany NY)
; 16(12): 10462-10476, 2024 06 17.
Article
em En
| MEDLINE
| ID: mdl-38889378
ABSTRACT
BACKGROUND:
Osteosarcoma is a highly malignant bone tumor that exhibits rapid growth and early metastasis. Hypoxia plays a pivotal role in promoting the proliferation and metastasis of osteosarcoma through a series of molecular events, which are partially mediated and regulated by HIF-1α. However, the regulatory network associated with HIF-1α in osteosarcoma remains limited. Therefore, the objective of this study was to identify critical hypoxia-associated genes and investigate their effects and molecular mechanisms in osteosarcoma cells.METHODS:
Through bioinformatics analysis, matrilin-4 (MATN4) was identified as a crucial gene associated with hypoxia. The expression of MATN4 and HIF-1α was assessed using immunohistochemistry, RT-qPCR, and western blotting. The proliferative capacity of osteosarcoma cells was assessed through the utilization of CCK-8, EDU staining, and colony formation assays. The effects of MATN4 on the mobility of OS cells were evaluated using wound-healing assays and transwell assays. The interaction between MATN4 and HIF-1α was detected through chromatin immunoprecipitation.RESULTS:
MATN4 is overexpressed in osteosarcoma tissue and cells, particularly in osteosarcoma cells with high metastatic potential. Knockdown of MATN4 inhibits the proliferation, migration, and invasion abilities of osteosarcoma cells and reverses the promoting effects of hypoxia on these functions. Additionally, HIF-1α binds to MATN4 and upregulates its expression. Interestingly, knockdown of HIF-1α reduces the stimulatory effects of MATN4 overexpression on the proliferation, migration, and invasion of osteosarcoma cells under hypoxic conditions.CONCLUSIONS:
Taken together, our results suggest that MATN4 is regulated by HIF-1α and confers a more aggressive phenotype on OS cells. This evidence suggests that MATN4 may act as a potential target for OS diagnosis and treatment.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ósseas
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Osteossarcoma
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Regulação Neoplásica da Expressão Gênica
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Proliferação de Células
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Subunidade alfa do Fator 1 Induzível por Hipóxia
Limite:
Humans
Idioma:
En
Revista:
Aging (Albany NY)
Assunto da revista:
GERIATRIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China