Pyroptosis-related gene GSDMC indicates poor prognosis and promotes tumor progression by activating the AKT/mTOR pathway in lung squamous cell carcinoma.
Mol Carcinog
; 63(11): 2218-2236, 2024 Nov.
Article
en En
| MEDLINE
| ID: mdl-39136610
ABSTRACT
Lung squamous cell carcinoma (LUSC) is one of the most common malignant tumors of the respiratory. Pyroptosis plays an essential role in cancer, but there is limited research investigating pyroptosis in LUSC. In this study, pyroptosis-related genes were observed to have extensive multiomics alterations in LUSC through analysis of the TCGA database. Utilizing machine learning for selection and verifying expression levels, GSDMC was chosen as the critical gene for further experiments. Our research found that GSDMC is overexpressed in LUSC tissues and cells, and is associated with poor prognosis. Knockdown of GSDMC in LUSC inhibits cell proliferation, invasion, metastasis, chemotherapeutic sensitivity, and reduced tumor formation in nude mice, accompanied by downregulation of proliferative and EMT-related protein expression. However, these effects were counteracted in cells where GSDMC is overexpressed. Mechanistically, the oncogenic role of GSDMC is primarily achieved through the activation of the AKT/mTOR pathway, and this effect can be significantly reversed by rapamycin. Finally, SMAD4's interaction with the promoter region of GSDMC results in the suppression of GSDMC expression. In summary, our study through bioinformatics and experimental approaches not only proves that SMAD4 regulates the protumorigenic role of GSDMC through transcriptional targeting, but also indicates the possibility of developing the SMAD4/GSDMC/AKT/mTOR signaling axis as a potential biomarker and treatment target for LUSC.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Carcinoma de Células Escamosas
/
Transducción de Señal
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Regulación Neoplásica de la Expresión Génica
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Proliferación Celular
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Proteínas Proto-Oncogénicas c-akt
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Serina-Treonina Quinasas TOR
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Piroptosis
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Neoplasias Pulmonares
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Ratones Desnudos
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Mol Carcinog
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos