Induction of the long noncoding RNA NBR2 from the bidirectional BRCA1 promoter under hypoxic conditions

J. Erin Wiedmeier, Anna Ohlrich, Adrian Chu, Michael R. Rountree, Mitchell Turker

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

BRCA1 plays an important role in preventing breast cancer and is often silenced or repressed in sporadic cancer. The BRCA1 promoter is bidirectional: it drives transcription of the long non-coding (lnc) NBR2 transcript in the opposite orientation relative to the BRCA1 transcript. Hypoxic conditions repress BRCA1 transcription, but their effect on expression of the NBR2 transcript has not been reported. We used quantitative RT-PCR to measure BRCA1 and NBR2 transcript levels in 0% and 1% oxygen in MCF-7 breast cancer cells and found that NBR2 transcript levels increased as a function of time under hypoxic conditions, whereas BRCA1 mRNA levels were repressed. Hypoxic conditions were ineffective in reducing BRCA1 mRNA in the UACC-3199 breast cancer cell line, which is reported to have an epigenetically silenced BRCA1 promoter, even though appreciable levels of BRCA1 and NBR2 mRNA were detected. Significant recovery back to baseline RNA levels occurred within 48 h after the MCF-7 cells were restored to normoxic conditions. We used a construct with the 218 bp minimal BRCA1 promoter linked to marker genes to show that this minimal promoter repressed expression bidirectionally under hypoxic conditions, which suggests that the elements necessary for induction of NBR2 are located elsewhere.

Original languageEnglish (US)
Pages (from-to)13-19
Number of pages7
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume796
DOIs
StatePublished - Feb 1 2017

Fingerprint

Long Noncoding RNA
Breast Neoplasms
Messenger RNA
MCF-7 Cells
RNA
Oxygen
Cell Line
Polymerase Chain Reaction
Genes
Neoplasms

Keywords

  • BRCA1
  • Hypoxia
  • lncRNA
  • NBR2

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

Cite this

Induction of the long noncoding RNA NBR2 from the bidirectional BRCA1 promoter under hypoxic conditions. / Wiedmeier, J. Erin; Ohlrich, Anna; Chu, Adrian; Rountree, Michael R.; Turker, Mitchell.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 796, 01.02.2017, p. 13-19.

Research output: Contribution to journalArticle

@article{0e33db28fa8c4c4a9e4b9cde084555de,
title = "Induction of the long noncoding RNA NBR2 from the bidirectional BRCA1 promoter under hypoxic conditions",
abstract = "BRCA1 plays an important role in preventing breast cancer and is often silenced or repressed in sporadic cancer. The BRCA1 promoter is bidirectional: it drives transcription of the long non-coding (lnc) NBR2 transcript in the opposite orientation relative to the BRCA1 transcript. Hypoxic conditions repress BRCA1 transcription, but their effect on expression of the NBR2 transcript has not been reported. We used quantitative RT-PCR to measure BRCA1 and NBR2 transcript levels in 0{\%} and 1{\%} oxygen in MCF-7 breast cancer cells and found that NBR2 transcript levels increased as a function of time under hypoxic conditions, whereas BRCA1 mRNA levels were repressed. Hypoxic conditions were ineffective in reducing BRCA1 mRNA in the UACC-3199 breast cancer cell line, which is reported to have an epigenetically silenced BRCA1 promoter, even though appreciable levels of BRCA1 and NBR2 mRNA were detected. Significant recovery back to baseline RNA levels occurred within 48 h after the MCF-7 cells were restored to normoxic conditions. We used a construct with the 218 bp minimal BRCA1 promoter linked to marker genes to show that this minimal promoter repressed expression bidirectionally under hypoxic conditions, which suggests that the elements necessary for induction of NBR2 are located elsewhere.",
keywords = "BRCA1, Hypoxia, lncRNA, NBR2",
author = "Wiedmeier, {J. Erin} and Anna Ohlrich and Adrian Chu and Rountree, {Michael R.} and Mitchell Turker",
year = "2017",
month = "2",
day = "1",
doi = "10.1016/j.mrfmmm.2017.02.001",
language = "English (US)",
volume = "796",
pages = "13--19",
journal = "Mutation Research",
issn = "1386-1964",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - Induction of the long noncoding RNA NBR2 from the bidirectional BRCA1 promoter under hypoxic conditions

AU - Wiedmeier, J. Erin

AU - Ohlrich, Anna

AU - Chu, Adrian

AU - Rountree, Michael R.

AU - Turker, Mitchell

PY - 2017/2/1

Y1 - 2017/2/1

N2 - BRCA1 plays an important role in preventing breast cancer and is often silenced or repressed in sporadic cancer. The BRCA1 promoter is bidirectional: it drives transcription of the long non-coding (lnc) NBR2 transcript in the opposite orientation relative to the BRCA1 transcript. Hypoxic conditions repress BRCA1 transcription, but their effect on expression of the NBR2 transcript has not been reported. We used quantitative RT-PCR to measure BRCA1 and NBR2 transcript levels in 0% and 1% oxygen in MCF-7 breast cancer cells and found that NBR2 transcript levels increased as a function of time under hypoxic conditions, whereas BRCA1 mRNA levels were repressed. Hypoxic conditions were ineffective in reducing BRCA1 mRNA in the UACC-3199 breast cancer cell line, which is reported to have an epigenetically silenced BRCA1 promoter, even though appreciable levels of BRCA1 and NBR2 mRNA were detected. Significant recovery back to baseline RNA levels occurred within 48 h after the MCF-7 cells were restored to normoxic conditions. We used a construct with the 218 bp minimal BRCA1 promoter linked to marker genes to show that this minimal promoter repressed expression bidirectionally under hypoxic conditions, which suggests that the elements necessary for induction of NBR2 are located elsewhere.

AB - BRCA1 plays an important role in preventing breast cancer and is often silenced or repressed in sporadic cancer. The BRCA1 promoter is bidirectional: it drives transcription of the long non-coding (lnc) NBR2 transcript in the opposite orientation relative to the BRCA1 transcript. Hypoxic conditions repress BRCA1 transcription, but their effect on expression of the NBR2 transcript has not been reported. We used quantitative RT-PCR to measure BRCA1 and NBR2 transcript levels in 0% and 1% oxygen in MCF-7 breast cancer cells and found that NBR2 transcript levels increased as a function of time under hypoxic conditions, whereas BRCA1 mRNA levels were repressed. Hypoxic conditions were ineffective in reducing BRCA1 mRNA in the UACC-3199 breast cancer cell line, which is reported to have an epigenetically silenced BRCA1 promoter, even though appreciable levels of BRCA1 and NBR2 mRNA were detected. Significant recovery back to baseline RNA levels occurred within 48 h after the MCF-7 cells were restored to normoxic conditions. We used a construct with the 218 bp minimal BRCA1 promoter linked to marker genes to show that this minimal promoter repressed expression bidirectionally under hypoxic conditions, which suggests that the elements necessary for induction of NBR2 are located elsewhere.

KW - BRCA1

KW - Hypoxia

KW - lncRNA

KW - NBR2

UR - http://www.scopus.com/inward/record.url?scp=85013947369&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85013947369&partnerID=8YFLogxK

U2 - 10.1016/j.mrfmmm.2017.02.001

DO - 10.1016/j.mrfmmm.2017.02.001

M3 - Article

C2 - 28249151

AN - SCOPUS:85013947369

VL - 796

SP - 13

EP - 19

JO - Mutation Research

JF - Mutation Research

SN - 1386-1964

ER -