The International Peace Maternity and Child Health Hospital, Shanghai Jiaotong University, Shanghai, China.
Cancer Sci. 2013 Dec;104(12):1683-9. doi: 10.1111/cas.12277. Epub 2013 Oct 22.
The important functions of heat shock factor 1 (HSF1) in certain malignant cancers have granted it to be an appealing target for developing novel strategy for cancer therapy. Here, we report that higher HSF1 expression is associated with more aggressive malignization in epithelial ovarian tumors, indicating that targeting HSF1 is also a promising strategy against ovarian cancer. We found that a nucleoside analog (Ly101-4B) elicits efficient inhibition on HSF1 expression and potent anticancer activity on epithelial ovarian cancer both in vitro and in vivo. Moreover, by targeting HSF1, Ly101-4B inhibits the biogenesis of microRNA-214, which has been revealed to be overexpressed and to promote cell survival in human ovarian epithelial tumors. These findings demonstrate that Ly101-4B is a promising candidate for ovarian cancer therapy, and expand our understanding of HSF1, by revealing that it can regulate microRNA biogenesis in addition to its canonical function of regulating protein-coding RNAs.
热休克因子 1（HSF1）在某些恶性肿瘤中的重要功能使其成为开发癌症治疗新策略的有吸引力的靶标。在这里，我们报告说，HSF1 表达水平较高与上皮性卵巢肿瘤的恶性程度增加有关，这表明靶向 HSF1 也是对抗卵巢癌的一种有前途的策略。我们发现核苷类似物（Ly101-4B）可有效抑制 HSF1 的表达，并在体外和体内对上皮性卵巢癌具有强大的抗癌活性。此外，通过靶向 HSF1，Ly101-4B 抑制了 microRNA-214 的生物发生，microRNA-214 在人类卵巢上皮性肿瘤中被发现过表达，并促进细胞存活。这些发现表明，Ly101-4B 是卵巢癌治疗的一种很有前途的候选药物，并通过揭示 HSF1 除了调节蛋白质编码 RNA 的经典功能外，还可以调节 microRNA 的生物发生，扩展了我们对 HSF1 的理解。
