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, Zuzana HOLUBCOVÁ, Josef JAROŠ, Petr DVOŘÁK, Šárka POSPÍŠILOVÁ and Aleš HAMPL. MicroRNAs Regulate p21(Waf1/Cip1) Protein Expression and the DNA Damage Response in Human Embryonic Stem Cells. Stem Cells. Miamisburg, Ohio: AlphaMed Press, 2012, vol. 30, No 7, p. 1362-1372. ISSN 1066-5099. Available from: https://dx.doi.org/10.1002/stem.1108.

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

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10600 1.6 Biological sciences
• Country of publisher: United States of America
• Confidentiality degree: is not subject to a state or trade secret
• Impact factor: Impact factor: 7.701
• RIV identification code: RIV/00216224:14110/12:00057498
• Organization unit: Faculty of Medicine
• Doi: http://dx.doi.org/10.1002/stem.1108
• UT WoS: 000305477000005
• Keywords in English: Human embryonic stem cells; microRNA; DNA damage; p21; CDKN1A; p53; miR-302
• Tags: International impact

Abstract

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