title: Nucleoside analog inhibits microRNA-214 through targeting heat-shock factor 1 in human epithelial ovarian cancer.
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.
authors.affiliation: The International Peace Maternity and Child Health Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yi-Fei
authors.initials: YF
authors.lastname: Chen
authors.forename: Zhangli
authors.initials: Z
authors.lastname: Dong
authors.forename: Yi
authors.initials: Y
authors.lastname: Xia
authors.forename: Jingjie
authors.initials: J
authors.lastname: Tang
authors.forename: Ling
authors.initials: L
authors.lastname: Peng
authors.forename: Shuying
authors.initials: S
authors.lastname: Wang
authors.forename: Dongmei
authors.initials: D
authors.lastname: Lai
mesh_terms: D000818:Animals; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics; D018832:Molecular Chaperones; D009368:Neoplasm Transplantation; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism*; D009705:Nucleosides / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D034622:RNA Interference; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C057725:HSPB1 protein, human; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C586901:Ly101-4B; C547397:MIRN214 microRNA, human; D035683:MicroRNAs; D018832:Molecular Chaperones; D009705:Nucleosides; D014157:Transcription Factors; D014230:Triazoles
references.citation: Cancer Res. 2008 Jan 15;68(2):425-33
references.pmid: 18199536
references.citation: Endocr Relat Cancer. 2010 Jan 29;17(1):F77-89
references.pmid: 19903743
references.citation: Clin Cancer Res. 2008 May 1;14(9):2690-5
references.pmid: 18451233
references.citation: Int J Clin Oncol. 2012 Oct;17(5):424-9
references.pmid: 22915194
references.citation: Stem Cells Dev. 2013 Jan 15;22(2):320-9
references.pmid: 22985337
references.citation: Cell Metab. 2011 Jul 6;14(1):91-103
references.pmid: 21723507
references.citation: Expert Opin Ther Targets. 2009 Apr;13(4):469-78
references.pmid: 19335068
references.citation: J Med Chem. 2009 Oct 8;52(19):6083-96
references.pmid: 19754200
references.citation: Biochem Biophys Res Commun. 2008 Dec 5;377(1):136-40
references.pmid: 18834857
references.citation: Int J Biochem Cell Biol. 2010 Aug;42(8):1262-72
references.pmid: 20035894
references.citation: J Cell Physiol. 2000 Mar;182(3):311-22
references.pmid: 10653597
references.citation: Cancer Sci. 2013 Dec;104(12):1683-9
references.pmid: 24033540
references.citation: Cancer. 2012 Apr 1;118(7):1782-94
references.pmid: 22009757
references.citation: Cell. 2012 Aug 3;150(3):549-62
references.pmid: 22863008
references.citation: Cancer Lett. 2013 Sep 10;338(1):147-57
references.pmid: 23138176
references.citation: Cancer Lett. 2012 May 28;318(2):145-53
references.pmid: 22266185
references.citation: Cell Cycle. 2009 Dec;8(23):3806-8
references.pmid: 19901525
references.citation: Oncogene. 2007 Aug 2;26(35):5086-97
references.pmid: 17310987
references.citation: Mini Rev Med Chem. 2010 Aug;10(9):806-21
references.pmid: 20482498
references.citation: Oncogene. 2010 Sep 16;29(37):5204-13
references.pmid: 20622894
references.citation: Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18378-83
references.pmid: 22042860
references.citation: Cancer Res. 2010 Mar 1;70(5):1906-15
references.pmid: 20179198
references.citation: Nat Rev Cancer. 2011 Nov 24;11(12):849-64
references.pmid: 22113163
references.citation: Cell. 2007 Sep 21;130(6):1005-18
references.pmid: 17889646
references.citation: Annu Rev Pathol. 2009;4:287-313
references.pmid: 18842102
references.citation: Drug Discov Today. 2013 Mar;18(5-6):282-9
references.pmid: 23064097
references.citation: Expert Opin Ther Targets. 2012 Aug;16(8):747-59
references.pmid: 22690697
references.citation: Nucleic Acids Res. 2009 May;37(9):2962-73
references.pmid: 19295133