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Risk SNP-Mediated Promoter-Enhancer Switching Drives Prostate Cancer through lncRNA PCAT19

The prostate cancer (PCa) risk-associated SNP rs11672691 is positively associated with aggressive disease at diagnosis. We showed that rs11672691 maps to the promoter of a short isoform of long noncoding RNA PCAT19 (PCAT19-short), which is in the third intron of the long isoform (PCAT19-long). The r... Full description

Journal Title: Cell 26 July 2018, Vol.174(3), pp.564-575.e18
Main Author: Hua, Junjie Tony
Other Authors: Ahmed, Musaddeque , Guo, Haiyang , Zhang, Yuzhe , Chen, Sujun , Soares, Fraser , Lu, Jennifer , Zhou, Stanley , Wang, Miranda , Li, Hui , Larson, Nicholas B , Mcdonnell, Shannon K , Patel, Parasvi S , Liang, Yi , Yao, Cindy Q , van Der Kwast, Theodorus , Lupien, Mathieu , Feng, Felix Y , Zoubeidi, Amina , Tsao, Ming-Sound
Format: Electronic Article Electronic Article
Language: English
Subjects:
Yy1
Yy1
ID: ISSN: 0092-8674 ; E-ISSN: 1097-4172 ; DOI: 10.1016/j.cell.2018.06.014
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recordid: elsevier_sdoi_10_1016_j_cell_2018_06_014
title: Risk SNP-Mediated Promoter-Enhancer Switching Drives Prostate Cancer through lncRNA PCAT19
format: Article
creator:
  • Hua, Junjie Tony
  • Ahmed, Musaddeque
  • Guo, Haiyang
  • Zhang, Yuzhe
  • Chen, Sujun
  • Soares, Fraser
  • Lu, Jennifer
  • Zhou, Stanley
  • Wang, Miranda
  • Li, Hui
  • Larson, Nicholas B
  • Mcdonnell, Shannon K
  • Patel, Parasvi S
  • Liang, Yi
  • Yao, Cindy Q
  • van Der Kwast, Theodorus
  • Lupien, Mathieu
  • Feng, Felix Y
  • Zoubeidi, Amina
  • Tsao, Ming-Sound
subjects:
  • Prostate Cancer Progression
  • Risk Snp
  • Lncrna
  • Bifunctional Regulatory Element
  • Promoter-Enhancer Switching
  • Rs11672691
  • Pcat19
  • Yy1
  • Nkx3.1
  • Hnrnpab
  • Prostate Cancer Progression
  • Risk Snp
  • Lncrna
  • Bifunctional Regulatory Element
  • Promoter-Enhancer Switching
  • Rs11672691
  • Pcat19
  • Yy1
  • Nkx3.1
  • Hnrnpab
ispartof: Cell, 26 July 2018, Vol.174(3), pp.564-575.e18
description: The prostate cancer (PCa) risk-associated SNP rs11672691 is positively associated with aggressive disease at diagnosis. We showed that rs11672691 maps to the promoter of a short isoform of long noncoding RNA PCAT19 (PCAT19-short), which is in the third intron of the long isoform (PCAT19-long). The risk variant is associated with decreased and increased levels of PCAT19-short and PCAT19-long, respectively. Mechanistically, the risk SNP region is bifunctional with both promoter and enhancer activity. The risk variants of rs11672691 and its LD SNP rs887391 decrease binding of transcription factors NKX3.1 and YY1 to the promoter of PCAT19-short, resulting in weaker promoter but stronger enhancer activity that subsequently activates PCAT19-long. PCAT19-long interacts with HNRNPAB to activate a subset of cell-cycle genes associated with PCa progression, thereby promoting PCa tumor growth and metastasis. Taken together, these findings reveal a risk SNP-mediated promoter-enhancer switching...
language: eng
source:
identifier: ISSN: 0092-8674 ; E-ISSN: 1097-4172 ; DOI: 10.1016/j.cell.2018.06.014
fulltext: fulltext
issn:
  • 0092-8674
  • 00928674
  • 1097-4172
  • 10974172
url: Link


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titleRisk SNP-Mediated Promoter-Enhancer Switching Drives Prostate Cancer through lncRNA PCAT19
creatorHua, Junjie Tony ; Ahmed, Musaddeque ; Guo, Haiyang ; Zhang, Yuzhe ; Chen, Sujun ; Soares, Fraser ; Lu, Jennifer ; Zhou, Stanley ; Wang, Miranda ; Li, Hui ; Larson, Nicholas B ; Mcdonnell, Shannon K ; Patel, Parasvi S ; Liang, Yi ; Yao, Cindy Q ; van Der Kwast, Theodorus ; Lupien, Mathieu ; Feng, Felix Y ; Zoubeidi, Amina ; Tsao, Ming-Sound
ispartofCell, 26 July 2018, Vol.174(3), pp.564-575.e18
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subjectProstate Cancer Progression ; Risk Snp ; Lncrna ; Bifunctional Regulatory Element ; Promoter-Enhancer Switching ; Rs11672691 ; Pcat19 ; Yy1 ; Nkx3.1 ; Hnrnpab ; Prostate Cancer Progression ; Risk Snp ; Lncrna ; Bifunctional Regulatory Element ; Promoter-Enhancer Switching ; Rs11672691 ; Pcat19 ; Yy1 ; Nkx3.1 ; Hnrnpab
descriptionThe prostate cancer (PCa) risk-associated SNP rs11672691 is positively associated with aggressive disease at diagnosis. We showed that rs11672691 maps to the promoter of a short isoform of long noncoding RNA PCAT19 (PCAT19-short), which is in the third intron of the long isoform (PCAT19-long). The risk variant is associated with decreased and increased levels of PCAT19-short and PCAT19-long, respectively. Mechanistically, the risk SNP region is bifunctional with both promoter and enhancer activity. The risk variants of rs11672691 and its LD SNP rs887391 decrease binding of transcription factors NKX3.1 and YY1 to the promoter of PCAT19-short, resulting in weaker promoter but stronger enhancer activity that subsequently activates PCAT19-long. PCAT19-long interacts with HNRNPAB to activate a subset of cell-cycle genes associated with PCa progression, thereby promoting PCa tumor growth and metastasis. Taken together, these findings reveal a risk SNP-mediated promoter-enhancer switching...
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titleRisk SNP-Mediated Promoter-Enhancer Switching Drives Prostate Cancer through lncRNA PCAT19
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The prostate cancer (PCa) risk-associated SNP rs11672691 is positively associated with aggressive disease at diagnosis. We showed that rs11672691 maps to the promoter of a short isoform of long noncoding RNA PCAT19 (PCAT19-short), which is in the third intron of the long isoform (PCAT19-long). The risk variant is associated with decreased and increased levels of PCAT19-short and PCAT19-long, respectively. Mechanistically, the risk SNP region is bifunctional with both promoter and enhancer activity. The risk variants of rs11672691 and its LD SNP rs887391 decrease binding of transcription factors NKX3.1 and YY1 to the promoter of PCAT19-short, resulting in weaker promoter but stronger enhancer activity that subsequently activates PCAT19-long. PCAT19-long interacts with HNRNPAB to activate a subset of cell-cycle genes associated with PCa progression, thereby promoting PCa tumor growth and metastasis. Taken together, these findings reveal a risk SNP-mediated promoter-enhancer switching...

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abstract

The prostate cancer (PCa) risk-associated SNP rs11672691 is positively associated with aggressive disease at diagnosis. We showed that rs11672691 maps to the promoter of a short isoform of long noncoding RNA PCAT19 (PCAT19-short), which is in the third intron of the long isoform (PCAT19-long). The risk variant is associated with decreased and increased levels of PCAT19-short and PCAT19-long, respectively. Mechanistically, the risk SNP region is bifunctional with both promoter and enhancer activity. The risk variants of rs11672691 and its LD SNP rs887391 decrease binding of transcription factors NKX3.1 and YY1 to the promoter of PCAT19-short, resulting in weaker promoter but stronger enhancer activity that subsequently activates PCAT19-long. PCAT19-long interacts with HNRNPAB to activate a subset of cell-cycle genes associated with PCa progression, thereby promoting PCa tumor growth and metastasis. Taken together, these findings reveal a risk SNP-mediated promoter-enhancer switching...

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