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BMC Cancer ; 24(1): 551, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693472

RESUMO

OBJECTIVE: We aimed to screen novel gene signatures for ovarian cancer (OC) and explore the role of biomarkers in OC via regulating pyroptosis using bioinformatics analysis. METHODS: Differentially expressed genes (DEGs) of OC were screened from GSE12470 and GSE16709 datasets. Hub genes were determined from protein-protein interaction networks after bioinformatics analysis. The role of Centromeric protein M (CENPM) in OC was assessed by subcutaneous tumor experiment using hematoxylin-eosin and immunohistochemical staining. Tumor metastasis was evaluated by detecting epithelial-mesenchymal transition-related proteins. The proliferation, migration, and invasion were determined using cell counting kit and transwell assay. Enzyme-linked immunosorbent assay was applied to measure inflammatory factors. The mRNA and protein expression were detected using real-time quantitative PCR and western blot. RESULTS: We determined 9 hub genes (KIFC1, PCLAF, CDCA5, KNTC1, MCM3, OIP5, CENPM, KIF15, and ASF1B) with high prediction value for OC. In SKOV3 and A2780 cells, the expression levels of hub genes were significantly up-regulated, compared with normal ovarian cells. CENPM was selected as a key gene. Knockdown of CENPM suppressed proliferation, migration, and invasion of OC cells. Subcutaneous tumor experiment revealed that CENPM knockdown significantly suppressed tumor growth and metastasis. Additionally, pyroptosis was promoted in OC cells and xenograft tumors after CENPM knockdown. Furthermore, CENPM knockdown activated cGAS-STING pathway and the pathway inhibitor reversed the inhibitory effect of CENPM knockdown on viability, migration, and invasion of OC cells. CONCLUSION: CENPM was a novel biomarker of OC, and knockdown of CENPM inhibited OC progression by promoting pyroptosis and activating cGAS-STING pathway.


Assuntos
Proteínas de Membrana , Nucleotidiltransferases , Neoplasias Ovarianas , Piroptose , Transdução de Sinais , Humanos , Feminino , Piroptose/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Animais , Camundongos , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genética , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Cromossômicas não Histona/metabolismo , Proteínas Cromossômicas não Histona/genética , Movimento Celular/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Nus
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