miR-34b-3p-mediated regulation of STC2 and FN1 enhances chemosensitivity and inhibits proliferation in cervical cancer.
Acta Biochim Biophys Sin (Shanghai)
; 56(5): 740-752, 2024 05 25.
Article
en En
| MEDLINE
| ID: mdl-38477044
ABSTRACT
Dysregulation of microRNA (miRNA) expression in cancer is a significant factor contributing to the progression of chemoresistance. The objective of this study is to explore the underlying mechanisms by which miR-34b-3p regulates chemoresistance in cervical cancer (CC). Previous findings have demonstrated low expression levels of miR-34b-3p in both CC chemoresistant cells and tissues. In this study, we initially characterize the behavior of SiHa/DDP cells which are CC cells resistant to the chemotherapeutic drug cisplatin (DDP). Subsequently, miR-34b-3p mimics are transfected into SiHa/DDP cells. It is observed that overexpression of miR-34b-3p substantially inhibits the proliferation, migration, and invasion abilities of SiHa/DDP cells and also enhances their sensitivity to DDP-induced cell death. Quantitative RT-PCR and western blot analysis further reveal elevated expression levels of STC2 and FN1 in SiHa/DDP cells, contrary to the expression pattern of miR-34b-3p. Moreover, STC2 and FN1 contribute to DDP resistance, proliferation, migration, invasion, and decreased apoptosis in CC cells. Through dual-luciferase assay analysis, we confirm that STC2 and FN1 are direct targets of miR-34b-3p in CC. Finally, rescue experiments demonstrate that overexpression of either STC2 or FN1 can partially reverse the inhibitory effects of miR-34b-3p overexpression on chemoresistance, proliferation, migration and invasion in CC cells. In conclusion, our findings support the role of miR-34b-3p as a tumor suppressor in CC. This study indicates that targeting the miR-34b-3p/STC2 or FN1 axis has potential therapeutic implications for overcoming chemoresistance in CC patients.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias del Cuello Uterino
/
Fibronectinas
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Cisplatino
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Resistencia a Antineoplásicos
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MicroARNs
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Proliferación Celular
Límite:
Female
/
Humans
Idioma:
En
Revista:
Acta Biochim Biophys Sin (Shanghai)
Asunto de la revista:
BIOFISICA
/
BIOQUIMICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China