SNAIL and miR-34a feed-forward regulation of ZNF281/ZBP99 promotes epithelial-mesenchymal transition.

Publisher: Wiley Blackwell Country of Publication: England NLM ID: 8208664 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1460-2075 (Electronic) Linking ISSN: 02614189 NLM ISO Abbreviation: EMBO J Subsets: MEDLINE

Publication: 2014- : London : Wiley Blackwell
Original Publication: Eynsham, Oxford, England : Published for the European Molecular Biology Organization by IRL Press, [c1982-

Epithelial-Mesenchymal Transition* ; Gene Expression Regulation, Neoplastic*; Breast Neoplasms/*pathology ; Colorectal Neoplasms/*pathology ; DNA-Binding Proteins/*metabolism ; MicroRNAs/*genetics ; Trans-Activators/*metabolism ; Transcription Factors/*metabolism; Animals ; Base Sequence ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Case-Control Studies ; Cell Movement ; Cells, Cultured ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/metabolism ; Female ; Fibroblasts/cytology ; Fibroblasts/metabolism ; Humans ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Lung Neoplasms/secondary ; Male ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Molecular Sequence Data ; Neoplasm Invasiveness ; Repressor Proteins ; Sequence Homology, Nucleic Acid ; Snail Family Transcription Factors ; Spheroids, Cellular/metabolism ; Spheroids, Cellular/pathology ; Tumor Suppressor Protein p53 ; Wound Healing

Here, we show that expression of ZNF281/ZBP-99 is controlled by SNAIL and miR-34a/b/c in a coherent feed-forward loop: the epithelial-mesenchymal transition (EMT) inducing factor SNAIL directly induces ZNF281 transcription and represses miR-34a/b/c, thereby alleviating ZNF281 mRNA from direct down-regulation by miR-34. Furthermore, p53 activation resulted in a miR-34a-dependent repression of ZNF281. Ectopic ZNF281 expression in colorectal cancer (CRC) cells induced EMT by directly activating SNAIL, and was associated with increased migration/invasion and enhanced β-catenin activity. Furthermore, ZNF281 induced the stemness markers LGR5 and CD133, and increased sphere formation. Conversely, experimental down-regulation of ZNF281 resulted in mesenchymal-epithelial transition (MET) and inhibition of migration/invasion, sphere formation and lung metastases in mice. Ectopic c-MYC induced ZNF281 protein expression in a SNAIL-dependent manner. Experimental inactivation of ZNF281 prevented EMT induced by c-MYC or SNAIL. In primary CRC samples, expression of ZNF281 increased during tumour progression and correlated with recurrence. Taken together, these results identify ZNF281 as a component of EMT-regulating networks, which contribute to metastasis formation in CRC.

Cancer Res. 2009 Jan 15;69(2):709-17. (PMID: 19147588)
Mol Cell. 2007 Jul 6;27(1):91-105. (PMID: 17612493)
Cell Cycle. 2012 Jan 15;11(2):215-6. (PMID: 22214667)
Nature. 2009 Jan 29;457(7229):603-7. (PMID: 19092805)
Int J Mol Med. 2007 Jun;19(6):967-70. (PMID: 17487431)
Mol Cell Biol. 2002 Feb;22(4):1184-93. (PMID: 11809809)
Nat Cell Biol. 2008 May;10(5):593-601. (PMID: 18376396)
Cell Transplant. 2013;22(1):29-40. (PMID: 22963690)
Eur J Cancer. 2009 Jul;45(11):2034-40. (PMID: 19403300)
Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):16202-7. (PMID: 22988117)
Cell. 2008 May 16;133(4):704-15. (PMID: 18485877)
Nat Cell Biol. 2000 Feb;2(2):84-9. (PMID: 10655587)
Br J Cancer. 2008 Oct 21;99(8):1285-9. (PMID: 18781171)
Cell. 2007 Dec 14;131(6):1109-23. (PMID: 18083101)
Nat Rev Cancer. 2007 Jun;7(6):415-28. (PMID: 17508028)
PLoS Biol. 2004 Nov;2(11):e363. (PMID: 15502875)
Nucleic Acids Res. 2005 Nov 24;33(20):6566-78. (PMID: 16314317)
Science. 2007 May 25;316(5828):1160-6. (PMID: 17525332)
Cell Stem Cell. 2013 May 2;12(5):602-15. (PMID: 23642368)
Cancer Res. 2008 Jun 1;68(11):4123-32. (PMID: 18519671)
Clin Cancer Res. 2013 Feb 1;19(3):710-20. (PMID: 23243217)
Nat Rev Cancer. 2012 Sep;12(9):613-26. (PMID: 22898542)
Cell Death Differ. 2004 Jun;11(6):663-73. (PMID: 14963412)
Biochem J. 2006 Mar 1;394(Pt 2):449-57. (PMID: 16232121)
Mol Cell Biol. 2001 Jul;21(14):4670-83. (PMID: 11416144)
Nat Rev Mol Cell Biol. 2002 Mar;3(3):155-66. (PMID: 11994736)
J Cell Sci. 2003 May 15;116(Pt 10):1959-67. (PMID: 12668723)
J Biol Chem. 2002 Oct 18;277(42):39209-16. (PMID: 12161443)
Cell. 2011 Oct 14;147(2):275-92. (PMID: 22000009)
Cancer Res. 2005 Jul 15;65(14):6237-44. (PMID: 16024625)
Stem Cells. 2008 Nov;26(11):2791-9. (PMID: 18757296)
J Cell Physiol. 2007 Nov;213(2):374-83. (PMID: 17680632)
Oncogene. 2004 Sep 23;23(44):7345-54. (PMID: 15286702)
EMBO J. 2012 Jun 12;31(14):3079-91. (PMID: 22692129)
Genes Dev. 2008 Apr 1;22(7):894-907. (PMID: 18381893)
Nat Cell Biol. 2009 Dec;11(12):1487-95. (PMID: 19935649)
Cancer Res. 2012 Sep 1;72(17):4597-608. (PMID: 22787120)
Cell Mol Life Sci. 2012 Oct;69(20):3429-56. (PMID: 22945800)
Cells Tissues Organs. 2005;179(1-2):56-65. (PMID: 15942193)
FEBS Lett. 2010 Jun 3;584(11):2231-6. (PMID: 20385133)
Biol Cell. 2005 Mar;97(3):185-96. (PMID: 15715524)
Nat Rev Cancer. 2006 Oct;6(10):813-23. (PMID: 16990858)
Nat Rev Cancer. 2002 Jun;2(6):442-54. (PMID: 12189386)
Nat Rev Cancer. 2013 Feb;13(2):97-110. (PMID: 23344542)
FEBS Lett. 1999 Jun 25;453(3):369-74. (PMID: 10405178)
Nat Protoc. 2009;4(11):1591-613. (PMID: 19834475)
J Exp Med. 2013 Jul 1;210(7):1331-50. (PMID: 23752226)
Nat Rev Cancer. 2005 Sep;5(9):744-9. (PMID: 16148886)
Gastroenterology. 2008 Mar;134(3):849-64. (PMID: 18325394)
Nature. 2007 Oct 25;449(7165):1003-7. (PMID: 17934449)
J Cell Biol. 2006 Mar 27;172(7):973-81. (PMID: 16567498)
J Cell Biol. 2011 Oct 31;195(3):417-33. (PMID: 22024162)
Cell Cycle. 2007 Jan 15;6(2):205-17. (PMID: 17314511)
Nature. 2006 Nov 16;444(7117):364-8. (PMID: 17093407)
Cell Cycle. 2011 Dec 15;10(24):4256-71. (PMID: 22134354)
Stem Cells. 2011 Nov;29(11):1705-16. (PMID: 21915945)
Nat Genet. 2008 Jan;40(1):43-50. (PMID: 18066065)
Biochem Biophys Res Commun. 1999 Aug 19;262(1):113-20. (PMID: 10448078)
EMBO Rep. 2011 Sep 30;12(10):1055-61. (PMID: 21909076)
Int J Colorectal Dis. 2010 May;25(5):583-90. (PMID: 20195621)
Nat Rev Cancer. 2009 Apr;9(4):265-73. (PMID: 19262571)
Mol Cell Biol. 2012 Jun;32(11):2054-64. (PMID: 22473993)
J Cell Sci. 1999 Apr;112 ( Pt 8):1237-45. (PMID: 10085258)
Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15339-44. (PMID: 9860970)
Neoplasia. 2004 Jan-Feb;6(1):1-6. (PMID: 15068665)
Development. 2006 Sep;133(18):3641-50. (PMID: 16914492)
Oncogene. 2010 Aug 5;29(31):4436-48. (PMID: 20543867)
Cancer Res. 2006 Sep 1;66(17):8319-26. (PMID: 16951136)
BMC Cancer. 2011 Sep 19;11:396. (PMID: 21929801)
Nucleic Acids Res. 1993 Aug 25;21(17):3951-7. (PMID: 8371971)
Gastroenterology. 2011 Jul;141(1):279-91, 291.e1-5. (PMID: 21640118)
Mamm Genome. 2006 Oct;17(10):999-1004. (PMID: 17019648)

0 (DNA-Binding Proteins)
0 (MIRN34 microRNA, human)
0 (MicroRNAs)
0 (Repressor Proteins)
0 (Snail Family Transcription Factors)
0 (TP53 protein, human)
0 (Trans-Activators)
0 (Transcription Factors)
0 (Tumor Suppressor Protein p53)
0 (ZNF148 protein, human)
0 (ZNF281 protein, human)

Date Created: 20131105 Date Completed: 20140128 Latest Revision: 20220321

20240829

PMC3844956

10.1038/emboj.2013.236

24185900