Estradiol-regulated microRNAs control estradiol response in breast cancer cells.
Estradiol-regulated microRNAs control estradiol response in breast cancer cells.
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DOI：
10.1093/nar/gkp500
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发表时间：
2009-08
影响因子：
14.9
通讯作者：
Nakshatri H
中科院分区：
文献类型：
--
作者：
Bhat-Nakshatri P;Wang G;Collins NR;Thomson MJ;Geistlinger TR;Carroll JS;Brown M;Hammond S;Srour EF;Liu Y;Nakshatri H
雌激素受体（E2）通过作为雌激素受体α（ERα）和雌激素受体β（ERβ）的配体在转录水平上调节基因表达。E2诱导蛋白c-Myc和E2 Fs分别是最佳ERα活性和次级雌激素反应所必需的。我们发现E2在MCF-7乳腺癌细胞中诱导了21种microRNA，并抑制了7种microRNA;这些microRNA有可能在转录后水平控制420种E2调节的mRNA和757种非E2调节的mRNA。丝氨酸/苏氨酸激酶AKT改变E2调节的microRNA表达。E2诱导了8个Let-7家族成员、miR-98和miR-21 microRNA的表达;这些microRNA降低了c-Myc和E2 F2蛋白的水平。Dicer是一种微小RNA加工所需的核糖核酸酶III，也是一种E2诱导基因。一些E2调节的microRNA基因与ERα结合位点相关或位于雌激素调节基因的基因内区域。我们认为ERα阳性乳腺癌的临床过程依赖于E2调节的肿瘤抑制microRNA和致癌microRNA之间的平衡。此外，我们的研究揭示了通过microRNA控制E2反应的负调控环以及E2诱导的转录组和蛋白质组的差异。
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.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
5.3
作者：
Hossain, Anwar;Kuo, Macus T.;Saunders, Grady F.
通讯作者：
Saunders, Grady F.
影响因子：
11.2
作者：
Johnson, Charles D.;Esquela-Kerscher, Aurora;Slack, Frank J.
通讯作者：
Slack, Frank J.
影响因子：
30.8
作者：
Chang, Tsung-Cheng;Yu, Duonan;Mendell, Joshua T.
通讯作者：
Mendell, Joshua T.
DOI：
10.1073/pnas.0803230105
发表时间：
2008-09-30
影响因子：
11.1
作者：
Forman, Joshua J.;Legesse-Miller, Aster;Coller, Hilary A.
通讯作者：
Coller, Hilary A.