The miR-199a-5p/HIF1α dual-regulatory axis participates in hypoxia-induced aggressive phenotypes of oral squamous cell carcinoma (OSCC) cells.
Int J Clin Oncol
; 29(9): 1244-1254, 2024 Sep.
Article
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| MEDLINE
| ID: mdl-38853186
ABSTRACT
BACKGROUND:
The late-stage diagnosis and distant metastasis of oral squamous cell carcinoma (OSCC) remain a huge challenge to clinical treatment for OSCC. During the past decades, targeting glycolysis-inducing factors becomes an attractive new strategy in OSCC therapies.METHODS:
OSCC cells were stimulated with hypoxia or transfected with agomir-199a-5p, antagomir-199a-5p, and siRNA for HIF1A, cell proliferation was detected by CCK-8 assay; HIF1α, GLUT1, HK2 and LDHA expression levels were examined with western blot; miR-199 expression was determined with RT-PCR; cell migratory and invasive abilities were examined using wound healing and transwell assays; the lactate and glucose in culture medium were also determined. Luciferase assay or CHIP assay was applied for confirm the binding between miR-199a-5p and HIF1A 3'UTR, or between HIF1α and miR-199a promoter.RESULTS:
HIF1α showed to be abnormally up-regulated, and miR-199a-5p showed to be abnormally down-regulated within OSCC under hypoxia. Hypoxia considerably enhanced OSCC cell proliferation, glycolysis, migratory ability, and invasive ability. MiR-199a-5p bound to HIF1A 3'-UTR and suppressed HIF1A expression; HIF1α targeted miR-199a-5p promoter region and downregulated miR-199a-5p expression. Under hypoxia, miR-199a-5p overexpression significantly repressed HIF1α up-regulation inresponse to hypoxia, OSCC cell proliferation, glycolysis, migratory ability, and invasive ability.CONCLUSION:
miR-199a-5p and HIF1α form a dual-regulatory axis in OSCC cells; the miR-199a-5p/HIF1α dual-regulatory axis contributes to hypoxia-induced aggressive OSCC phenotypes.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Boca
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Carcinoma de Células Escamosas
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Regulación Neoplásica de la Expresión Génica
/
Movimiento Celular
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MicroARNs
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Proliferación Celular
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Subunidad alfa del Factor 1 Inducible por Hipoxia
Límite:
Humans
Idioma:
En
Revista:
Int J Clin Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Japón