Repository logo
 

Estradiol-regulated microRNAs control estradiol response in breast cancer cells.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Bhat-Nakshatri, Poornima 
Wang, Guohua 
Collins, Nikail R 
Thomson, Michael J 
Geistlinger, Tim R 

Abstract

Estradiol (E2) regulates gene expression at the transcriptional level by functioning as a ligand for estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta). E2-inducible proteins c-Myc and E2Fs are required for optimal ERalpha 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 ERalpha-binding sites or located in the intragenic region of estrogen-regulated genes. We propose that the clinical course of ERalpha-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.

Description

Keywords

Binding Sites, Breast Neoplasms, Cell Line, Tumor, E2F Transcription Factors, Estradiol, Estrogen Receptor alpha, Female, Gene Expression Regulation, Neoplastic, Humans, MicroRNAs, Proto-Oncogene Proteins c-akt, Proto-Oncogene Proteins c-myc, Regulatory Elements, Transcriptional, Ribonuclease III

Journal Title

Nucleic Acids Res

Conference Name

Journal ISSN

0305-1048
1362-4962

Volume Title

37

Publisher

Oxford University Press (OUP)