Post-transcriptional regulation of BRCA2 through interactions with miR-19a and miR-19b
Breast cancer type 2, early onset susceptibility gene (BRCA2) is a major component of the homologous recombination DNA repair pathway. It acts as a tumor suppressor whose function is often lost in cancers. Patients with specific mutations in the BRCA2 gene often display discrete clinical, histopatho...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-08-01
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| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fgene.2016.00143/full |
| _version_ | 1811337966704918528 |
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| author | Elena Mogilyansky Peter Clark Kevin Quann Honglei Zhou Eric Londin Yi Jing Isidore Rigoutsos |
| author_facet | Elena Mogilyansky Peter Clark Kevin Quann Honglei Zhou Eric Londin Yi Jing Isidore Rigoutsos |
| author_sort | Elena Mogilyansky |
| collection | DOAJ |
| description | Breast cancer type 2, early onset susceptibility gene (BRCA2) is a major component of the homologous recombination DNA repair pathway. It acts as a tumor suppressor whose function is often lost in cancers. Patients with specific mutations in the BRCA2 gene often display discrete clinical, histopathological and molecular features. However, a subset of sporadic cancers has wild type BRCA2 and display defects in the Homology-Directed Repair (HDR) pathway, which is the hallmark of ‘BRCAness’. The mechanisms by which BRCAness arises are not fully understood but post-transcriptional regulation of BRCA2 gene expression by microRNAs (miRNAs) may contribute to this phenotype. Here, we examine the post-transcriptional effects that some members of the six-miRNA cluster known as the miR-17/92 cluster have on the abundance of BRCA2’s messenger RNA (mRNA) and protein. We discuss two interactions involving the miR-19a and miR-19b members of the cluster and the 3´UTR of BRCA2’s mRNA. We investigated these miRNA:mRNA interactions in fifteen cell lines derived from pancreatic, breast, colon, and kidney tissue. We show that over-expression of these two miRNAs results in a concomitant decrease of BRCA2’s mRNA and protein expression in a subset of the tested cell lines. Additionally, using luciferase reporter assays we identified direct interactions between miR-19a/miR-19b and a miRNA response element (MRE) in BRCA2’s 3´UTR. Our results suggest that BRCA2 is subject to a complex post-transcriptional regulatory program that has specific dependencies on the genetic and phenotypic background of cell types. |
| first_indexed | 2024-04-13T18:02:42Z |
| format | Article |
| id | doaj.art-818a382ff8994b1bae8037c8fcb1581c |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-13T18:02:42Z |
| publishDate | 2016-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-818a382ff8994b1bae8037c8fcb1581c2022-12-22T02:36:11ZengFrontiers Media S.A.Frontiers in Genetics1664-80212016-08-01710.3389/fgene.2016.00143210094Post-transcriptional regulation of BRCA2 through interactions with miR-19a and miR-19bElena Mogilyansky0Peter Clark1Kevin Quann2Honglei Zhou3Eric Londin4Yi Jing5Isidore Rigoutsos6Thomas Jefferson UniversityThe Children’s Hospital of PhiladelphiaSidney Kimmel Medical College, Thomas Jefferson UniversityThomas Jefferson UniversityThomas Jefferson UniversityThomas Jefferson UniversityThomas Jefferson UniversityBreast cancer type 2, early onset susceptibility gene (BRCA2) is a major component of the homologous recombination DNA repair pathway. It acts as a tumor suppressor whose function is often lost in cancers. Patients with specific mutations in the BRCA2 gene often display discrete clinical, histopathological and molecular features. However, a subset of sporadic cancers has wild type BRCA2 and display defects in the Homology-Directed Repair (HDR) pathway, which is the hallmark of ‘BRCAness’. The mechanisms by which BRCAness arises are not fully understood but post-transcriptional regulation of BRCA2 gene expression by microRNAs (miRNAs) may contribute to this phenotype. Here, we examine the post-transcriptional effects that some members of the six-miRNA cluster known as the miR-17/92 cluster have on the abundance of BRCA2’s messenger RNA (mRNA) and protein. We discuss two interactions involving the miR-19a and miR-19b members of the cluster and the 3´UTR of BRCA2’s mRNA. We investigated these miRNA:mRNA interactions in fifteen cell lines derived from pancreatic, breast, colon, and kidney tissue. We show that over-expression of these two miRNAs results in a concomitant decrease of BRCA2’s mRNA and protein expression in a subset of the tested cell lines. Additionally, using luciferase reporter assays we identified direct interactions between miR-19a/miR-19b and a miRNA response element (MRE) in BRCA2’s 3´UTR. Our results suggest that BRCA2 is subject to a complex post-transcriptional regulatory program that has specific dependencies on the genetic and phenotypic background of cell types.http://journal.frontiersin.org/Journal/10.3389/fgene.2016.00143/fullDNA RepairCancerBRCA1BRCA2post-transcriptional regulationMicroRNA (miRNA) |
| spellingShingle | Elena Mogilyansky Peter Clark Kevin Quann Honglei Zhou Eric Londin Yi Jing Isidore Rigoutsos Post-transcriptional regulation of BRCA2 through interactions with miR-19a and miR-19b Frontiers in Genetics DNA Repair Cancer BRCA1 BRCA2 post-transcriptional regulation MicroRNA (miRNA) |
| title | Post-transcriptional regulation of BRCA2 through interactions with miR-19a and miR-19b |
| title_full | Post-transcriptional regulation of BRCA2 through interactions with miR-19a and miR-19b |
| title_fullStr | Post-transcriptional regulation of BRCA2 through interactions with miR-19a and miR-19b |
| title_full_unstemmed | Post-transcriptional regulation of BRCA2 through interactions with miR-19a and miR-19b |
| title_short | Post-transcriptional regulation of BRCA2 through interactions with miR-19a and miR-19b |
| title_sort | post transcriptional regulation of brca2 through interactions with mir 19a and mir 19b |
| topic | DNA Repair Cancer BRCA1 BRCA2 post-transcriptional regulation MicroRNA (miRNA) |
| url | http://journal.frontiersin.org/Journal/10.3389/fgene.2016.00143/full |
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