MicroRNA-Specificity Protein (Sp) Transcription Factor Interactions and Significance in Carcinogenesis.

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 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 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 miRNASp TF axis can be highly effective for cancer chemotherapy.