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Cancer Sci. 2013 Dec;104(12):1683-9. doi: 10.1111/cas.12277. Epub 2013 Oct 22.

Nucleoside analog inhibits microRNA-214 through targeting heat-shock factor 1 in human epithelial ovarian cancer.

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  • 1The International Peace Maternity and Child Health Hospital, Shanghai Jiaotong University, Shanghai, China.

Abstract

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.

© 2013 Japanese Cancer Association.

PMID:
24033540
[PubMed - indexed for MEDLINE]
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