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

Cell death & disease(2023)

引用 0|浏览33
暂无评分
摘要
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.
更多
查看译文
关键词
Cancer,Translational research,Life Sciences,general,Biochemistry,Cell Biology,Immunology,Cell Culture,Antibodies
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要