高温腹腔化疗（HIPEC）能增加局部药物浓度并减少与长期腹腔暴露治疗相关的系统副作用，适用于腹腔恶性肿瘤或来源于胃、结肠、肾脏和卵巢原发性肿瘤的转移疾病患者。目前对HIPEC的抗癌机制研究较少。本研究发现，HIPEC治疗可以促进卵巢腹腔转移病灶患者miR-145-5p的表达，并显著下调其致癌靶基因c-MYC，EGFR，OCT4和MUC1。通过对HIPEC治疗患者卵巢腹腔转移结节的RNA测序分析发现，HSF-1是miR-145-5p表达的转录调节因子。值得注意的是，HSF-1表达缺失或其转录活性的化学抑制都会影响42°C下培养的卵巢癌细胞系中miR-145-5p的肿瘤抑制活性和对顺铂的反应。综上所述，我们的研究结果揭示了一个新的转录网络，涉及到HSF-1、miR145-5p、MYC、EGFR、MUC1和OCT4的相互作用，这些因子的正常活性有助于HIPEC治疗卵巢转移腹腔病灶的抗癌效果。©2023. 作者。

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.© 2023. The Author(s).