Abstract:
RATIONALE:MicroRNAs modestly suppress their direct mRNA targets, and these direct effects are amplified by modulation of gene transcription pathways. Consequently, indirect mRNA modulatory effects of microRNAs to increase or decrease mRNAs greatly outnumber direct target suppressions. Because microRNAs are products of transcription, the potential exists for microRNAs that regulate transcription to regulate other microRNAs. OBJECTIVE:Determine whether cardiac-expressed microRNAs regulate expression of other cardiac microRNAs, and measure the impact of microRNA-mediated microRNA regulation on indirect regulation of nontarget mRNAs. METHODS AND RESULTS:Transgenic expression of pre-microRNAs was used to generate mouse hearts expressing 6- to 16-fold normal levels of microRNA (miR)-143, miR-378, and miR-499. Genome-wide mRNA and microRNA signatures were established using deep sequencing; expression profiles provoked by each microRNA were defined. miR-143 suppressed its direct cardiac mRNA target hexokinase 2, but exhibited little indirect target regulation and did not regulate other cardiac microRNAs. Both miR-378 and miR-499 indirectly regulated hundreds of cardiac mRNAs and 15 to 30 cardiac microRNAs. MicroRNA overexpression did not alter normal processing of either transgenic or endogenous cardiac microRNAs, and microRNA-mediated regulation of other microRNAs encoded within parent genes occurred in tandem with parent mRNAs. MicroRNA regulation by miR-378 and miR-499 was stimulus specific, and contributed to observed mRNA downregulation. CONCLUSIONS:MicroRNAs that modulate cardiac transcription can indirectly regulate other microRNAs. Transcriptional modulation by microRNAs, and microRNA-mediated microRNA regulation, help explain how small direct effects of microRNAs are amplified to generate striking phenotypes.
journal_name
Circ Resjournal_title
Circulation researchauthors
Matkovich SJ,Hu Y,Dorn GW 2nddoi
10.1161/CIRCRESAHA.113.300975subject
Has Abstractpub_date
2013-06-21 00:00:00pages
62-71issue
1eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.113.300975journal_volume
113pub_type
杂志文章abstract::This study examines the cellular basis and specificity of the effects of adenosine on early afterdepolarizations (EADs), delayed afterdepolarizations (DADs), and triggered activity (TA) induced by various drugs with different mechanisms of action. Membrane potential and currents were measured in isolated guinea pig ve...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.70.4.743
更新日期:1992-04-01 00:00:00
abstract:RATIONALE:Prospective cohort studies question the value of HDL-C (high-density lipoprotein cholesterol) for stroke risk prediction. OBJECTIVE:Investigate the relationship between long-term functional recovery and HDL proteome and function. METHODS AND RESULTS:Changes in HDL protein composition and function (cholester...
journal_title:Circulation research
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doi:10.1161/CIRCRESAHA.120.316526
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pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.111.262899
更新日期:2012-08-03 00:00:00
abstract::Angiotensin II (Ang II) has profound effects in the central nervous system (CNS), including promotion of thirst, regulation of vasopressin secretion, and modulation of sympathetic outflow. Despite its importance in cardiovascular and volume homeostasis, angiotensinergic mechanisms are incompletely understood in the CN...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000043501.47934.fa
更新日期:2002-11-29 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000159389.55544.20
更新日期:2005-03-18 00:00:00
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journal_title:Circulation research
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doi:10.1161/CIRCRESAHA.112.273946
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doi:10.1161/CIRCRESAHA.117.311185
更新日期:2017-09-29 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.199166
更新日期:2009-07-02 00:00:00
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journal_title:Circulation research
pub_type: 评论,杂志文章
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pub_type: 杂志文章
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更新日期:1999-05-14 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.69.3.582
更新日期:1991-09-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.58.2.292
更新日期:1986-02-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.192443
更新日期:2009-07-02 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章,评审
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更新日期:2014-07-07 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.185843
更新日期:2009-01-30 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.2.436
更新日期:1989-08-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.305347
更新日期:2015-04-10 00:00:00
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pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.119.315037
更新日期:2019-08-16 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.197228
更新日期:2009-05-22 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.1.9
更新日期:1992-07-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:
更新日期:1977-05-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2002-11-01 00:00:00
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journal_title:Circulation research
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更新日期:2021-01-08 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.44.1.23
更新日期:1979-01-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:2016-02-05 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh1101.091190
更新日期:2001-06-08 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.64.5.882
更新日期:1989-05-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:2006-05-12 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.6.199
更新日期:1975-06-01 00:00:00
abstract::The influence that the pressure-sensitive receptors in the cardiovascular system have on renal nerve activity and on heart rate was compared in normotensive rats (NTR) and spontaneously hypertensive rats (SHR). The cardiovascular receptors were stimulated by raising the blood pressure (BP) with intravenous phenylephri...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.40.6.571
更新日期:1977-06-01 00:00:00