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.

Breast cancer (BC) is the most common cancer among women worldwide. BRCA1/2 are responsible for 16–20% of the risk for hereditary BC. Other susceptibility genes have been identified; Fanconi Anemia Complementation Group M (FANCM) being one of these. Two variants in FANCM, rs144567652 and rs147021911, are associated with BC risk. These variants have been described in Finland, Italy, France, Spain, Germany, Australia, the United States, Sweden, Finnish, and the Netherlands, but not in the South American populations. Our study evaluated the association of the SNPs rs144567652 and rs147021911 with BC risk in non-carriers of BRCA1/2 mutations from a South American population. The SNPs were genotyped in 492 BRCA1/2-negative BC cases and 673 controls. Our data do not support an association between FANCM rs147021911 and rs144567652 SNPs and BC risk. Nevertheless, two BC cases, one with a family history of BC and the other with sporadic early-onset BC, were C/T heterozygotes for rs144567652. In conclusion, this is the first study related contribution of FANCM mutations and BC risk in a South American population. Nevertheless, more studies are necessary to evaluate if rs144567652 could be responsible for familial BC in BRCA1/2-negatives and for early-onset non-familial BC in Chilean BC cases.