Pituitary tumortransforming gene 1 regulates the senescence and apoptosis of oral squamous cell carcinoma in a p21dependent DNA damage response manner.
Oncol Rep
; 52(4)2024 10.
Article
en En
| MEDLINE
| ID: mdl-39155881
ABSTRACT
Pituitary tumortransforming gene 1 (PTTG1), also known as securin, is a protooncogene involved in the development of various cancers by promoting cell proliferation and mobility. However, its underlying biological mechanisms in oral squamous cell carcinoma (OSCC) progression remain unclear. in the present study, it was sought to elucidate the role of PTTG1 as an oncogene in OSCC progression and was attempted to unravel the underlying mechanism and impact of PTTG1 expression on cell cycle, cell death, and cellular senescence. The effect of double strand break on PTTG1 expression was investigated in OSCC growth. To identify the role of PTTG1 in OSCC growth, the cell viability and senescence was analyzed by EdU and senescenceassociated betagalactosidase (SAßgal) assay, respectively. To verify the DNA damageinduced senescence of PTTG1, the chromosomal damage in OSCC was analyzed in vitro. Finally, the effect of PTTG1 on tumor growth and gene expression related to cell viability and DNA damagedinduced senescence was investigated in vivo. PTTG1 expression was compared between OSCC and healthy patient samples (n=32) using reverse transcriptionquantitative PCR and immunohistochemistry; and it was found that PTTG1 expression was upregulated in OSCC. Small interfering RNAmediated knockdown of PTTG1 in two OSCC cell lines revealed that PTTG1 downregulation significantly inhibited cell proliferation and arrested the cell cycle pathway as evidenced by changes in checkpoint genes (such as cyclin D1, E and B1). PTTG1 knockdown also increased apoptosis, as evidenced by the upregulation of apoptotic genes [such as cleaved (c) Caspase7 and cpoly (ADPribose) polymerase]. Moreover, PTTG1 downregulation promoted cellular senescence, as shown by western blotting and SAßgal staining. Finally, senescenceinduced DNA damage was observed in OSCC cells, which accelerates genomic instability, through chromosomal damage analysis. Taken together, the present findings suggested that PTTG1 acts as a protooncogene; regulates cell proliferation, cell cycle, cellular senescence and DNA damage in OSCC; and may serve as a novel diagnostic biomarker and potential therapeutic target for OSCC.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Daño del ADN
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Neoplasias de la Boca
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Carcinoma de Células Escamosas
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Regulación Neoplásica de la Expresión Génica
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Senescencia Celular
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Apoptosis
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Proliferación Celular
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Inhibidor p21 de las Quinasas Dependientes de la Ciclina
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Securina
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Proto-Oncogenes Mas
Límite:
Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Oncol Rep
Asunto de la revista:
NEOPLASIAS
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Grecia