Estradiol-regulated microRNAs control estradiol response in breast cancer cells

Poornima Bhat-Nakshatri, Guohua Wang, Nikail R. Collins, Michael J. Thomson, Tim R. Geistlinger, Jason S. Carroll, Myles Brown, Scott Hammond, Edward Srour, Yunlong Liu, Harikrishna Nakshatri

Research output: Contribution to journalArticle

223 Citations (Scopus)

Abstract

Estradiol (E2) regulates gene expression at the transcriptional level by functioning as a ligand for estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). E2-inducible proteins c-Myc and E2Fs are required for optimal ERα activity and secondary estrogen responses, respectively. We show that E2 induces 21 microRNAs and represses seven microRNAs in MCF-7 breast cancer cells; these microRNAs have the potential to control 420 E2-regulated and 757 non-E2-regulated mRNAs at the post-transcriptional level. The serine/threonine kinase, AKT, alters E2-regulated expression of microRNAs. E2 induced the expression of eight Let-7 family members, miR-98 and miR-21 microRNAs; these microRNAs reduced the levels of c-Myc and E2F2 proteins. Dicer, a ribonuclease III enzyme required for microRNA processing, is also an E2-inducible gene. Several E2-regulated microRNA genes are associated with ERα-binding sites or located in the intragenic region of estrogen-regulated genes. We propose that the clinical course of ERα-positive breast cancers is dependent on the balance between E2-regulated tumor-suppressor microRNAs and oncogenic microRNAs. Additionally, our studies reveal a negative-regulatory loop controlling E2 response through microRNAs as well as differences in E2-induced transcriptome and proteome.

Original languageEnglish
Pages (from-to)4850-4861
Number of pages12
JournalNucleic Acids Research
Volume37
Issue number14
DOIs
StatePublished - 2009

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MicroRNAs
Estradiol
Breast Neoplasms
Estrogen Receptor alpha
Proto-Oncogene Proteins c-myc
E2F2 Transcription Factor
Estrogens
Ribonuclease III
Genes
Estrogen Receptor beta
Protein-Serine-Threonine Kinases
Proteome
Transcriptome
Binding Sites
Ligands
Gene Expression
Messenger RNA

ASJC Scopus subject areas

  • Genetics

Cite this

Bhat-Nakshatri, P., Wang, G., Collins, N. R., Thomson, M. J., Geistlinger, T. R., Carroll, J. S., ... Nakshatri, H. (2009). Estradiol-regulated microRNAs control estradiol response in breast cancer cells. Nucleic Acids Research, 37(14), 4850-4861. https://doi.org/10.1093/nar/gkp500

Estradiol-regulated microRNAs control estradiol response in breast cancer cells. / Bhat-Nakshatri, Poornima; Wang, Guohua; Collins, Nikail R.; Thomson, Michael J.; Geistlinger, Tim R.; Carroll, Jason S.; Brown, Myles; Hammond, Scott; Srour, Edward; Liu, Yunlong; Nakshatri, Harikrishna.

In: Nucleic Acids Research, Vol. 37, No. 14, 2009, p. 4850-4861.

Research output: Contribution to journalArticle

Bhat-Nakshatri, P, Wang, G, Collins, NR, Thomson, MJ, Geistlinger, TR, Carroll, JS, Brown, M, Hammond, S, Srour, E, Liu, Y & Nakshatri, H 2009, 'Estradiol-regulated microRNAs control estradiol response in breast cancer cells', Nucleic Acids Research, vol. 37, no. 14, pp. 4850-4861. https://doi.org/10.1093/nar/gkp500
Bhat-Nakshatri P, Wang G, Collins NR, Thomson MJ, Geistlinger TR, Carroll JS et al. Estradiol-regulated microRNAs control estradiol response in breast cancer cells. Nucleic Acids Research. 2009;37(14):4850-4861. https://doi.org/10.1093/nar/gkp500
Bhat-Nakshatri, Poornima ; Wang, Guohua ; Collins, Nikail R. ; Thomson, Michael J. ; Geistlinger, Tim R. ; Carroll, Jason S. ; Brown, Myles ; Hammond, Scott ; Srour, Edward ; Liu, Yunlong ; Nakshatri, Harikrishna. / Estradiol-regulated microRNAs control estradiol response in breast cancer cells. In: Nucleic Acids Research. 2009 ; Vol. 37, No. 14. pp. 4850-4861.
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