J 2012

MicroRNAs Regulate p21(Waf1/Cip1) Protein Expression and the DNA Damage Response in Human Embryonic Stem Cells

DOLEŽALOVÁ, Dáša, Marek MRÁZ, Tomáš BÁRTA, Karla PLEVOVÁ, Vladimír VINARSKÝ et. al.

Basic information

Original name

MicroRNAs Regulate p21(Waf1/Cip1) Protein Expression and the DNA Damage Response in Human Embryonic Stem Cells

Authors

DOLEŽALOVÁ, Dáša (703 Slovakia, belonging to the institution), Marek MRÁZ (203 Czech Republic, belonging to the institution), Tomáš BÁRTA (203 Czech Republic, belonging to the institution), Karla PLEVOVÁ (203 Czech Republic, belonging to the institution), Vladimír VINARSKÝ (203 Czech Republic, belonging to the institution), Zuzana HOLUBCOVÁ (203 Czech Republic, belonging to the institution), Josef JAROŠ (203 Czech Republic, belonging to the institution), Petr DVOŘÁK (203 Czech Republic, belonging to the institution), Šárka POSPÍŠILOVÁ (203 Czech Republic, belonging to the institution) and Aleš HAMPL (203 Czech Republic, guarantor, belonging to the institution)

Edition

Stem Cells, Miamisburg, Ohio, AlphaMed Press, 2012, 1066-5099

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10600 1.6 Biological sciences

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 7.701

RIV identification code

RIV/00216224:14110/12:00057498

Organization unit

Faculty of Medicine

DOI

UT WoS

000305477000005

Keywords in English

Human embryonic stem cells; microRNA; DNA damage; p21; CDKN1A; p53; miR-302

Tags

International impact
Změněno: 13/2/2013 22:06, Ing. Mgr. Věra Pospíšilíková

Abstract

V originále

Studies of human embryonic stem cells (hESCs) commonly describe the nonfunctional p53-p21 axis of the G1/S checkpoint pathway with subsequent relevance for cell cycle regulation and the DNA damage response (DDR). Importantly, p21 mRNA is clearly present and upregulated after the DDR in hESCs, but p21 protein is not detectable. In this article, we provide evidence that expression of p21 protein is directly regulated by the microRNA (miRNA) pathway under standard culture conditions and after DNA damage. The DDR in hESCs leads to upregulation of tens of miRNAs, including hESC-specific miRNAs such as those of the miR-302 family, miR-371-372 family, or C19MC miRNA cluster. Most importantly, we show that the hESC-enriched miRNA family miR-302 (miR-302a, miR-302b, miR-302c, and miR-302d) directly contributes to regulation of p21 expression in hESCs and, thus, demonstrate a novel function for miR-302s in hESCS. The described mechanism elucidates the role of miRNAs in regulation of important molecular pathway governing the G1/S transition checkpoint before as well as after DNA damage. STEM CELLS 2012;30:1362-1372

Links

ED1.1.00/02.0068, research and development project
Name: CEITEC - central european institute of technology
GAP301/10/1971, research and development project
Name: Exprese, signalizace a funkce receptorů smrti v lidských embryonálních kmenových buňkách.
Investor: Czech Science Foundation
MSM0021622430, plan (intention)
Name: Funkční a molekulární charakteristiky nádorových a normálních kmenových buněk - identifikace cílů pro nová terapeutika a terapeutické strategie
Investor: Ministry of Education, Youth and Sports of the CR, Functional and molecular characteristics of cancer and normal stem cells - identification of targets for novel therapeutics and therapeutic strategies
NT11218, research and development project
Name: Funkční a strukturní změny microRNA u lymfoproliferativních malignit a jejich vliv na prognózu onemocnění a predikci léčebné odpovědi

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