TY - JOUR
T1 - MicroRNA-Specificity Protein (Sp) Transcription Factor Interactions and Significance in Carcinogenesis
AU - Safe, Stephen
N1 - Funding Information:
The funding support of the Syd Kyle Endowment and the National Institutes of Health (P30ES023512) is gratefully acknowledged.
Publisher Copyright:
© 2015, Springer International Publishing AG.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - Specificity protein (Sp) transcription factors (TFs) such as Sp1, Sp3, and Sp4 are overexpressed in tumors, and Sp1 is a negative prognostic factor for multiple tumor types. Sp TFs regulate the expression of pro-oncogenic factors important for cell proliferation, survival, angiogenesis, migration/invasion, and inflammation, and the high expression of Sp TFs in tumors is primarily due to microRNAs (miRNAs). For example, expression of tumor-suppressor-like miRNAs such as miR-200b/c, miR-335, miR-22, miR-149, and others that inactivate Sp1 expression is low in many tumor types. Research in our laboratory has also demonstrated that high expression of Sp TFs is also due to miRNA-dependent inhibition of the transcriptional repressors ZBTB10 and ZBTB4 by miR-27a and miR-20a/miR-17p, respectively. Thus, miRNAs play a critical role in maintaining high levels of Sp1, Sp3, Sp4, and pro-oncogenic Sp-regulated genes in tumors and cancer cells, and there is ample evidence that anticancer agents targeting the miRNA-Sp TF axis can be highly effective for cancer chemotherapy.
AB - Specificity protein (Sp) transcription factors (TFs) such as Sp1, Sp3, and Sp4 are overexpressed in tumors, and Sp1 is a negative prognostic factor for multiple tumor types. Sp TFs regulate the expression of pro-oncogenic factors important for cell proliferation, survival, angiogenesis, migration/invasion, and inflammation, and the high expression of Sp TFs in tumors is primarily due to microRNAs (miRNAs). For example, expression of tumor-suppressor-like miRNAs such as miR-200b/c, miR-335, miR-22, miR-149, and others that inactivate Sp1 expression is low in many tumor types. Research in our laboratory has also demonstrated that high expression of Sp TFs is also due to miRNA-dependent inhibition of the transcriptional repressors ZBTB10 and ZBTB4 by miR-27a and miR-20a/miR-17p, respectively. Thus, miRNAs play a critical role in maintaining high levels of Sp1, Sp3, Sp4, and pro-oncogenic Sp-regulated genes in tumors and cancer cells, and there is ample evidence that anticancer agents targeting the miRNA-Sp TF axis can be highly effective for cancer chemotherapy.
KW - Sp TFs regulation
KW - Sp1
KW - Sp3
KW - Sp4
KW - Specificity protein transcription factors (Sp TFs)
KW - miR-20a/miR-17-5p:ZBTB4
KW - miR-27a:ZBT10
KW - miRNAs inhibit Sp TFs
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UR - http://www.scopus.com/inward/citedby.url?scp=84955582684&partnerID=8YFLogxK
U2 - 10.1007/s40495-014-0012-8
DO - 10.1007/s40495-014-0012-8
M3 - Review article
AN - SCOPUS:84955582684
VL - 1
SP - 73
EP - 78
JO - Current Pharmacology Reports
JF - Current Pharmacology Reports
SN - 2198-641X
IS - 2
ER -