期刊
NUCLEIC ACIDS RESEARCH
卷 37, 期 14, 页码 4850-4861出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkp500
关键词
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资金
- Department of Defense [BC053295]
- National Institutes of Health [R01CA89153]
- IU Simon Cancer Center [R01DK074967]
- NCI
- DFCI Women's Cancers Program
- Institutional funds
Estradiol (E2) regulates gene expression at the transcriptional level by functioning as a ligand for estrogen receptor alpha (ER alpha) and estrogen receptor beta (ER beta). E2-inducible proteins c-Myc and E2Fs are required for optimal ER alpha 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 ER alpha-binding sites or located in the intragenic region of estrogen-regulated genes. We propose that the clinical course of ER alpha-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.
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