Estrogen receptor {beta}1 expression is regulated by miR-92 in breast cancer

Hakeemah Al-Nakhle; Philip A Burns; Michele Cummings; Andrew M Hanby; Thomas A Hughes; Sampoorna Satheesha; Abeer M Shaaban; Laura Smith; Valerie Speirs

doi:10.1158/0008-5472.CAN-09-4104

Estrogen receptor {beta}1 expression is regulated by miR-92 in breast cancer

Hakeemah Al-Nakhle, Philip A Burns, Michele Cummings, Andrew M Hanby, Thomas A Hughes, Sampoorna Satheesha, Abeer M Shaaban, Laura Smith, Valerie Speirs

University of Leeds

Research output: Contribution to journal › Article › peer-review

103 Citations (Scopus)

Abstract

Estrogen receptor beta1 (ERbeta1) downregulation occurs in many breast cancers, but the responsible molecular mechanisms remain unclear. Here, we report that levels of ERbeta1 expression are negatively regulated by the microRNA miR-92. Expression analysis in a cohort of primary breast tumors confirmed a significant negative correlation between miR-92 and both ERbeta1 mRNA and protein. Inhibition of miR-92 in MCF-7 cells increased ERbeta1 expression in a dose-dependent manner, whereas miR-92 overexpression led to ERbeta1 downregulation. Reporter constructs containing candidate miR-92 binding sites in the 3'-untranslated region (UTR) of ERbeta1 suggested by bioinformatics analysis confirmed that miR-92 downregulated ERbeta1 via direct targeting of its 3'-UTR. Our results define a potentially important mechanism for downregulation of ERbeta1 expression in breast cancer.

Original language	English
Pages (from-to)	4778-84
Number of pages	7
Journal	Cancer Research
Volume	70
Issue number	11
DOIs	https://doi.org/10.1158/0008-5472.CAN-09-4104
Publication status	Published - 1 Jun 2010
Externally published	Yes

Keywords

3' Untranslated Regions
Binding Sites
Breast Neoplasms
Cell Line, Tumor
Estradiol
Estrogen Receptor beta
Female
Gene Expression Regulation, Neoplastic
Humans
MicroRNAs
Tamoxifen
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1158/0008-5472.CAN-09-4104

Cite this

@article{e34b368bfd3c4ad8be22c47fe0fdaeb0,

title = "Estrogen receptor {beta}1 expression is regulated by miR-92 in breast cancer",

abstract = "Estrogen receptor beta1 (ERbeta1) downregulation occurs in many breast cancers, but the responsible molecular mechanisms remain unclear. Here, we report that levels of ERbeta1 expression are negatively regulated by the microRNA miR-92. Expression analysis in a cohort of primary breast tumors confirmed a significant negative correlation between miR-92 and both ERbeta1 mRNA and protein. Inhibition of miR-92 in MCF-7 cells increased ERbeta1 expression in a dose-dependent manner, whereas miR-92 overexpression led to ERbeta1 downregulation. Reporter constructs containing candidate miR-92 binding sites in the 3'-untranslated region (UTR) of ERbeta1 suggested by bioinformatics analysis confirmed that miR-92 downregulated ERbeta1 via direct targeting of its 3'-UTR. Our results define a potentially important mechanism for downregulation of ERbeta1 expression in breast cancer.",

keywords = "3' Untranslated Regions, Binding Sites, Breast Neoplasms, Cell Line, Tumor, Estradiol, Estrogen Receptor beta, Female, Gene Expression Regulation, Neoplastic, Humans, MicroRNAs, Tamoxifen, Journal Article, Research Support, U.S. Gov't, Non-P.H.S.",

author = "Hakeemah Al-Nakhle and Burns, {Philip A} and Michele Cummings and Hanby, {Andrew M} and Hughes, {Thomas A} and Sampoorna Satheesha and Shaaban, {Abeer M} and Laura Smith and Valerie Speirs",

year = "2010",

month = jun,

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doi = "10.1158/0008-5472.CAN-09-4104",

language = "English",

volume = "70",

pages = "4778--84",

journal = "Cancer Research",

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TY - JOUR

T1 - Estrogen receptor {beta}1 expression is regulated by miR-92 in breast cancer

AU - Al-Nakhle, Hakeemah

AU - Burns, Philip A

AU - Cummings, Michele

AU - Hanby, Andrew M

AU - Hughes, Thomas A

AU - Satheesha, Sampoorna

AU - Shaaban, Abeer M

AU - Smith, Laura

AU - Speirs, Valerie

PY - 2010/6/1

Y1 - 2010/6/1

N2 - Estrogen receptor beta1 (ERbeta1) downregulation occurs in many breast cancers, but the responsible molecular mechanisms remain unclear. Here, we report that levels of ERbeta1 expression are negatively regulated by the microRNA miR-92. Expression analysis in a cohort of primary breast tumors confirmed a significant negative correlation between miR-92 and both ERbeta1 mRNA and protein. Inhibition of miR-92 in MCF-7 cells increased ERbeta1 expression in a dose-dependent manner, whereas miR-92 overexpression led to ERbeta1 downregulation. Reporter constructs containing candidate miR-92 binding sites in the 3'-untranslated region (UTR) of ERbeta1 suggested by bioinformatics analysis confirmed that miR-92 downregulated ERbeta1 via direct targeting of its 3'-UTR. Our results define a potentially important mechanism for downregulation of ERbeta1 expression in breast cancer.

AB - Estrogen receptor beta1 (ERbeta1) downregulation occurs in many breast cancers, but the responsible molecular mechanisms remain unclear. Here, we report that levels of ERbeta1 expression are negatively regulated by the microRNA miR-92. Expression analysis in a cohort of primary breast tumors confirmed a significant negative correlation between miR-92 and both ERbeta1 mRNA and protein. Inhibition of miR-92 in MCF-7 cells increased ERbeta1 expression in a dose-dependent manner, whereas miR-92 overexpression led to ERbeta1 downregulation. Reporter constructs containing candidate miR-92 binding sites in the 3'-untranslated region (UTR) of ERbeta1 suggested by bioinformatics analysis confirmed that miR-92 downregulated ERbeta1 via direct targeting of its 3'-UTR. Our results define a potentially important mechanism for downregulation of ERbeta1 expression in breast cancer.

KW - 3' Untranslated Regions

KW - Binding Sites

KW - Breast Neoplasms

KW - Cell Line, Tumor

KW - Estradiol

KW - Estrogen Receptor beta

KW - Female

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - MicroRNAs

KW - Tamoxifen

KW - Journal Article

KW - Research Support, U.S. Gov't, Non-P.H.S.

U2 - 10.1158/0008-5472.CAN-09-4104

DO - 10.1158/0008-5472.CAN-09-4104

M3 - Article

C2 - 20484043

SN - 0008-5472

VL - 70

SP - 4778

EP - 4784

JO - Cancer Research

JF - Cancer Research

IS - 11

ER -

Estrogen receptor {beta}1 expression is regulated by miR-92 in breast cancer

Abstract

Keywords

UN SDGs

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