RESUMO
Aggressive triple-negative breast cancer (TNBC) still lacks approved targeted therapies, requiring more exploration of its underlying mechanisms. Previous studies have suggested a potential role of SAT1 (Spermidine/Spermine N1-acetyltransferase 1) in cancer, which needs to be further elucidated in breast cancer. In this study, highly expressed SAT1 in TNBC signified worse patient prognoses. And SAT1 knockdown effectively inhibited the proliferation and migration abilities of TNBC cells in vitro and in vivo. In terms of mechanism, the transcription factor JUN enhanced SAT1 transcriptional activity by binding to its promoter region. Then, SAT1 protein in the cytoplasm engaged in directly binding with YBX1 for sustaining YBX1 protein stability via deubiquitylation mediated by the E3 ligase HERC5. Further, SAT1 was found to suppress autophagy remarkably via stabilization of mTOR mRNA with the accumulation of YBX1-mediated methyl-5-cytosine (m5C) modification. These findings proved that SAT1 drives TNBC progression through the SAT1/YBX1/mTOR axis, which may provide a potential candidate for targeted therapy in advanced TNBC.
Assuntos
Autofagia , Progressão da Doença , Neoplasias de Mama Triplo Negativas , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Humanos , Feminino , Autofagia/genética , Camundongos , Linhagem Celular Tumoral , Animais , Acetiltransferases/genética , Acetiltransferases/metabolismo , Modelos Animais de Doenças , Proliferação de Células/genética , Proteína 1 de Ligação a Y-Box/metabolismo , Proteína 1 de Ligação a Y-Box/genética , Regulação Neoplásica da Expressão Gênica/genética , Camundongos NusRESUMO
OBJECTIVES: Nasopharyngeal adenocarcinomas (NPACs) are rare malignant tumors. The treatment of NPACs is usually surgery with resection of normal nasal passage tissues.We introduced an innovative double endoscopic surgery for NPACs patients and evaluated the clinical efficacy of this approach. METHODS: The clinical data of 4 NPACs patients who underwent radical endoscopic nasopharyngectomy using a combined transnasal and transoral approach were analyzed to determine the efficacy of this surgery. The endpoints were en bloc resection and relief of clinical symptoms. RESULTS: All surgeries were successfully performed without any severe postoperative complications or death. Postoperative MRI revealed that en bloc resection was achieved for all patients with NPACs, and they had high quality of life without postoperative complications. CONCLUSIONS: The transnasal-transoral approach to endoscopic nasopharyngectomy for nasopharyngeal adenocarcinoma is safe and effective.