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 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.