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Cell Death Dis ; 14(8): 535, 2023 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-37598177

RESUMO

Hyperthermic intraperitoneal administration of chemotherapy (HIPEC) increases local drug concentrations and reduces systemic side effects associated with prolonged adjuvant intraperitoneal exposure in patients affected by either peritoneal malignancies or metastatic diseases originating from gastric, colon, kidney, and ovarian primary tumors. Mechanistically, the anticancer effects of HIPEC have been poorly explored. Herein we documented that HIPEC treatment promoted miR-145-5p expression paired with a significant downregulation of its oncogenic target genes c-MYC, EGFR, OCT4, and MUC1 in a pilot cohort of patients with ovarian peritoneal metastatic lesions. RNA sequencing analyses of ovarian peritoneal metastatic nodules from HIPEC treated patients unveils HSF-1 as a transcriptional regulator factor of miR-145-5p expression. Notably, either depletion of HSF-1 expression or chemical inhibition of its transcriptional activity impaired miR-145-5p tumor suppressor activity and the response to cisplatin in ovarian cancer cell lines incubated at 42 °C. In aggregate, our findings highlight a novel transcriptional network involving HSF-1, miR145-5p, MYC, EGFR, MUC1, and OCT4 whose proper activity contributes to HIPEC anticancer efficacy in the treatment of ovarian metastatic peritoneal lesions.


Assuntos
MicroRNAs , Neoplasias Ovarianas , Humanos , Feminino , Quimioterapia Intraperitoneal Hipertérmica , Genes myc , Fatores de Transcrição de Choque Térmico/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Fatores de Transcrição/genética , Linhagem Celular , Receptores ErbB , MicroRNAs/genética
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