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The miR-17/92 cluster: a comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease.

Mogilyansky E, Rigoutsos I - Cell Death Differ. (2013)

Bottom Line: The miR-17/92 cluster is among the best-studied microRNA clusters.Interest in the cluster and its members has been increasing steadily and the number of publications has grown exponentially since its discovery with more than 1000 articles published in 2012 alone.In light of its ever-increasing importance and ever-widening regulatory roles, we review here the latest body of knowledge on the cluster's involvement in health and disease as well as provide a novel perspective on the full spectrum of protein-coding and non-coding transcripts that are likely regulated by its members.

View Article: PubMed Central - PubMed

Affiliation: Computational Medicine Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.

ABSTRACT
The miR-17/92 cluster is among the best-studied microRNA clusters. Interest in the cluster and its members has been increasing steadily and the number of publications has grown exponentially since its discovery with more than 1000 articles published in 2012 alone. Originally found to be involved in tumorigenesis, research work in recent years has uncovered unexpected roles for its members in a wide variety of settings that include normal development, immune diseases, cardiovascular diseases, neurodegenerative diseases and aging. In light of its ever-increasing importance and ever-widening regulatory roles, we review here the latest body of knowledge on the cluster's involvement in health and disease as well as provide a novel perspective on the full spectrum of protein-coding and non-coding transcripts that are likely regulated by its members.

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Related in: MedlinePlus

The transcriptional regulation and main targets of the miR-17/92 cluster and its paralogues. The transcriptional factors (TFs) in the left upper corner have been functionally validated; dark blue arrows indicate upregulation; black lines indicate repression. TFs in the blue ‘cloud' were identified by the ENCODE project and the relationship of most of them to the miR-17/92 cluster and its paralogues is putative. Blue TFs were validated previously and confirmed by ENCODE; red TFs putatively regulate the miR-17/92 cluster and at the same time are known to be targeted by cluster members; green TFs putatively regulate the miR-17/92 cluster and at the same time are known to be targeted by paralogue miR-106b/25. If the specific gene that is targeted by a miRNA is known, the repressor line ends at the gene; otherwise, it ends at the box boundary of the respective cell process
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fig4: The transcriptional regulation and main targets of the miR-17/92 cluster and its paralogues. The transcriptional factors (TFs) in the left upper corner have been functionally validated; dark blue arrows indicate upregulation; black lines indicate repression. TFs in the blue ‘cloud' were identified by the ENCODE project and the relationship of most of them to the miR-17/92 cluster and its paralogues is putative. Blue TFs were validated previously and confirmed by ENCODE; red TFs putatively regulate the miR-17/92 cluster and at the same time are known to be targeted by cluster members; green TFs putatively regulate the miR-17/92 cluster and at the same time are known to be targeted by paralogue miR-106b/25. If the specific gene that is targeted by a miRNA is known, the repressor line ends at the gene; otherwise, it ends at the box boundary of the respective cell process

Mentions: Additional information on transcriptional regulation became available through the recent release by the ENCODE (Encyclopedia of DNA Elements) project25 of data from the study of 118 transcription factors (TFs). ENCODE's results revealed 1292 TF:miRNA interactions and 421 miRNA:TF interactions that in turn suggest tightly coupled auto-regulatory loops involving miRNAs and TFs. Of the 118 TFs, 34 pertain to the miR-17/92 cluster: they include the previously known MYC17, 18 and MXI26, 27 and 32 novel TFs (Figure 4). Among the newly identified TFs, BCL3 was found to regulate miR-17/92 and miR-106b/25. Further, BCL3, IRF1, SP1, TAL1 and ZBTB33 are targeted by individual miRNAs of the cluster, in addition to being TFs for the cluster (Figure 4). Moreover, several novel targets for members of miR-17/92 and miR-106b/25 were identified and are also summarized in Figure 4.25, 28 With regard to the miR-106a/363 cluster, it is likely regulated by the microphthalmia-associated transcription factor (MITF) through a binding site at position 133,135,780 (hg19) of chromosome X in the cluster's immediate vicinity.29


The miR-17/92 cluster: a comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease.

Mogilyansky E, Rigoutsos I - Cell Death Differ. (2013)

The transcriptional regulation and main targets of the miR-17/92 cluster and its paralogues. The transcriptional factors (TFs) in the left upper corner have been functionally validated; dark blue arrows indicate upregulation; black lines indicate repression. TFs in the blue ‘cloud' were identified by the ENCODE project and the relationship of most of them to the miR-17/92 cluster and its paralogues is putative. Blue TFs were validated previously and confirmed by ENCODE; red TFs putatively regulate the miR-17/92 cluster and at the same time are known to be targeted by cluster members; green TFs putatively regulate the miR-17/92 cluster and at the same time are known to be targeted by paralogue miR-106b/25. If the specific gene that is targeted by a miRNA is known, the repressor line ends at the gene; otherwise, it ends at the box boundary of the respective cell process
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3824591&req=5

fig4: The transcriptional regulation and main targets of the miR-17/92 cluster and its paralogues. The transcriptional factors (TFs) in the left upper corner have been functionally validated; dark blue arrows indicate upregulation; black lines indicate repression. TFs in the blue ‘cloud' were identified by the ENCODE project and the relationship of most of them to the miR-17/92 cluster and its paralogues is putative. Blue TFs were validated previously and confirmed by ENCODE; red TFs putatively regulate the miR-17/92 cluster and at the same time are known to be targeted by cluster members; green TFs putatively regulate the miR-17/92 cluster and at the same time are known to be targeted by paralogue miR-106b/25. If the specific gene that is targeted by a miRNA is known, the repressor line ends at the gene; otherwise, it ends at the box boundary of the respective cell process
Mentions: Additional information on transcriptional regulation became available through the recent release by the ENCODE (Encyclopedia of DNA Elements) project25 of data from the study of 118 transcription factors (TFs). ENCODE's results revealed 1292 TF:miRNA interactions and 421 miRNA:TF interactions that in turn suggest tightly coupled auto-regulatory loops involving miRNAs and TFs. Of the 118 TFs, 34 pertain to the miR-17/92 cluster: they include the previously known MYC17, 18 and MXI26, 27 and 32 novel TFs (Figure 4). Among the newly identified TFs, BCL3 was found to regulate miR-17/92 and miR-106b/25. Further, BCL3, IRF1, SP1, TAL1 and ZBTB33 are targeted by individual miRNAs of the cluster, in addition to being TFs for the cluster (Figure 4). Moreover, several novel targets for members of miR-17/92 and miR-106b/25 were identified and are also summarized in Figure 4.25, 28 With regard to the miR-106a/363 cluster, it is likely regulated by the microphthalmia-associated transcription factor (MITF) through a binding site at position 133,135,780 (hg19) of chromosome X in the cluster's immediate vicinity.29

Bottom Line: The miR-17/92 cluster is among the best-studied microRNA clusters.Interest in the cluster and its members has been increasing steadily and the number of publications has grown exponentially since its discovery with more than 1000 articles published in 2012 alone.In light of its ever-increasing importance and ever-widening regulatory roles, we review here the latest body of knowledge on the cluster's involvement in health and disease as well as provide a novel perspective on the full spectrum of protein-coding and non-coding transcripts that are likely regulated by its members.

View Article: PubMed Central - PubMed

Affiliation: Computational Medicine Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.

ABSTRACT
The miR-17/92 cluster is among the best-studied microRNA clusters. Interest in the cluster and its members has been increasing steadily and the number of publications has grown exponentially since its discovery with more than 1000 articles published in 2012 alone. Originally found to be involved in tumorigenesis, research work in recent years has uncovered unexpected roles for its members in a wide variety of settings that include normal development, immune diseases, cardiovascular diseases, neurodegenerative diseases and aging. In light of its ever-increasing importance and ever-widening regulatory roles, we review here the latest body of knowledge on the cluster's involvement in health and disease as well as provide a novel perspective on the full spectrum of protein-coding and non-coding transcripts that are likely regulated by its members.

Show MeSH
Related in: MedlinePlus