2. Academic Validation
  3. HSF-1/miR-145-5p transcriptional axis enhances hyperthermic intraperitoneal chemotherapy efficacy on peritoneal ovarian carcinosis

HSF-1/miR-145-5p transcriptional axis enhances hyperthermic intraperitoneal chemotherapy efficacy on peritoneal ovarian carcinosis

  • Cell Death Dis. 2023 Aug 19;14(8):535. doi: 10.1038/s41419-023-06064-9.
Silvia Di Agostino 1,  Valeria Canu 2,  Sara Donzelli 2,  Claudio Pulito 2,  Andrea Sacconi 3,  Federica Ganci 2,  Fabio Valenti 2,  Frauke Goeman 4,  Stefano Scalera 4,  Francesca Rollo 5,  Anna Bagnato 6,  Maria Grazia Diodoro 5,  Enrico Vizza 7,  Mariantonia Carosi 5,  Beatrice Rufini 2,  Orietta Federici 8,  Manuel Giofrè 8,  Fabio Carboni 8,  Paola Muti 9,  Gennaro Ciliberto 10,  Sabrina Strano 4,  Mario Valle 8,  Giovanni Blandino 11
Affiliations

Affiliations

  • 1 Department of Health Sciences, Magna Græcia University of Catanzaro, 88100, Catanzaro, Italy.
  • 2 Translational Oncology Research Unit, Department of Research, Diagnosis and Innovative Technologies, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
  • 3 Clinical Trial Center, Biostatistics and Bioinformatics Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
  • 4 SAFU Unit, Department of Research, Diagnosis and Innovative Technologies, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
  • 5 Department of Pathology, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
  • 6 Preclinical Models and New Therapeutic Agents Unit, IRCCS-Regina Elena National Cancer Institute, Rome, Italy.
  • 7 Gynecologic Oncology Unit, Department of Experimental Clinical Oncology, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
  • 8 Department of Digestive Surgery, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
  • 9 Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
  • 10 Scientific Direction, IRCCS Regina Elena National Cancer Institute, 00144, Rome, Italy.
  • 11 Translational Oncology Research Unit, Department of Research, Diagnosis and Innovative Technologies, IRCCS Regina Elena National Cancer Institute, Rome, Italy. [email protected].
PMID: 37598177 DOI: 10.1038/s41419-023-06064-9
Abstract

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.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-138280
    99.58%, HSF1 Inhibitor
    HSP