Abstract
Transcriptional coactivators play a key role in RNA polymerase II transcription and gene regulation. One of the most important transcriptional coactivators is the Mediator (MED) complex, which is an evolutionary conserved large multiprotein complex. MED transduces the signal between DNA-bound transcriptional activators (gene-specific transcription factors) to the RNA polymerase II transcription machinery to activate transcription. It is known that MED plays an essential role in ER-mediated gene expression mainly through the MED1 subunit, since estrogen receptor (ER) can interact with MED1 by specific protein–protein interactions; therefore, MED1 plays a fundamental role in ER-positive breast cancer (BC) etiology. Additionally, other MED subunits also play a role in BC etiology. On the other hand, microRNAs (miRNAs) are a family of small non-coding RNAs, which can regulate gene expression at the post-transcriptional level by binding in a sequence-specific fashion at the 3′ UTR of the messenger RNA. The miRNAs are also important factors that influence oncogenic signaling in BC by acting as both tumor suppressors and oncogenes. Moreover, miRNAs are involved in endocrine therapy resistance of BC, specifically to tamoxifen, a drug that is used to target ER signaling. In metazoans, very little is known about the transcriptional regulation of miRNA by the MED complex and less about the transcriptional regulation of miRNAs involved in BC initiation and progression. Recently, it has been shown that MED1 is able to regulate the transcription of the ER-dependent miR-191/425 cluster promoting BC cell proliferation and migration. In this review, we will discuss the role of MED1 transcriptional coactivator in the etiology of BC and in endocrine therapy-resistance of BC and also the contribution of other MED subunits to BC development, progression and metastasis. Lastly, we identified miRNAs that potentially can regulate the expression of MED subunits.
Highlights
MicroRNAs are small non-coding RNAs of 17–25 nucleotides in length that control gene expression in a post-transcriptional fashion
A genomic analysis of miRNAs in the human chromosome 19 miRNA cluster (C19MC) has revealed that those miRNAs are interspersed between Alu repeats and Alu transcription is dependent on the RNA polymerase III transcription machinery
MiRNAs are known to be aberrantly expressed in cancer, including breast cancer (BC), and some of them can act as tumor suppressors and others functioning as oncogenes which depends on the gene or pathway they regulate
Summary
MicroRNAs (miRNAs) are small non-coding RNAs of 17–25 nucleotides in length that control gene expression in a post-transcriptional fashion. They are master regulators of gene expression, which control gene expression via either messenger RNA (mRNA) translational repression or mRNA degradation [1,2]. The C19MC miRNAs are expected to constitute the 3 end of Alu transcripts when expressed. This evidence indicates that some of the miRNAs can be transcribed by RNA polymerase III in primates [8]. We will summarize the role of miRNAs in regulating the expression of MED complex subunits
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