A crossroad of microRNAs and immediate early genes (IEGs) encoding oncogenic transcription factors in breast cancer.
Signaling networks are involved in development, as well as in malignancy of the mammary gland. Distinct external stimuli activate intricate signaling cascades, which culminate in the activation of specific transcriptional programs. These signal-specific transcriptional programs are instigated by transcription factors (TFs) encoded by the immediate early genes (IEGs), and they lead to diverse cellular outcomes, including oncogenesis. Hence, regulating the expression of IEGs is of great importance, and involves several complementary transcriptional and posttranscriptional mechanisms, the latter entails also microRNAs (miRNAs). miRNAs are a class of non-coding RNAs, which have been implicated in regulation of various aspects of signaling networks. Through examination of the basic characteristics of miRNA function, we highlight the benefits of using miRNAs as regulators of early TFs and signaling networks. We further focus on the role of miRNAs as regulators of IEGs, which shape the initial steps of signaling-induced transcription. We especially emphasize the role of miRNAs in buffering external noise and maintaining low basal activation of IEGs in the absence of proper stimuli.
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, 76100, Israel.
Aldema
A
Sas-Chen
Roi
R
Avraham
Yosef
Y
Yarden
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D017781:Genes, Immediate-Early; D006801:Humans; D042361:Mammary Glands, Human / Q000254:growth & development / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
D035683:MicroRNAs; D014157:Transcription Factors