ATM B regulated miR-18a, adversely Chtigt the DNA-Sch Reaction by the ataxia telangiectasia mutated down-regulation of kinase Libing Song1., Chuyong Lin2., Zhiqiang WU2, Gong2 Hui Yong Zeng1, Jueheng WU3, Li2 Li3 first Mengfeng LY2608204 1234703-40-2 June * State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Cancer Center, Sun Yat-sen University t, Guangzhou, Guangdong, China, 2 Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University t, Guangzhou, Guangdong, China, 3 Institute of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University t, Guangzhou, Guangdong, China Abstract The DNA-Sch the reaction takes place in several steps by which cells to Sch the to develop DNA sense and transduce the signal to repair slightly damaged digter to initiate DNA.
Ataxia telangiectasia mutated kinase, as the prime Re sensor and signal converter DNA-Sch Has the functions shown to play an R Important prevention CEP-18770 Proteasome Inhibitors in the GDR and Krebspr. Therefore, the fully understand the molecular mechanisms of regulation of ATM again U much attention. Here we found that miR-18a, in both cell lines and tissue samples obtained from patients ht � Breast cancer. Furthermore, we demonstrated that ectopic expression of miR-18a expression by directly ATM to ATM-39-UTR and represses lifted the IR-induced cell cycle arrest. Similar to the effect of ATM siRNA, miR-18a overexpression in breast cancer cells reduced the F Ability of DNA repair and Besch Ending the efficiency of DNA repair and homologous sensitized cells recombinationbased c-irradiation.
However, the inhibition of miR-18a leads to an increased Hten DNA repair, h Cellular efficiency and lower HRR here Re radiosensitivity. In addition, we have shown that the H He phorsphorylation and nuclear foci formation of H2AX and 53BP1, the downstream Rts of ATM kinase substrates, were significantly deceased in the cells overexpressing miR-18a. Taken together, our results discovered a new mechanism of regulation of expression and ATM suggest that miR-18a k Nnte be a new therapeutic target. Quote: Song L, Lin C. Wu Z, Falun H, Zeng Y, et al. miR-18a, the DNA-Sch reaction by the ataxia telangiectasia mutated down-regulation of kinase adversely mighty. PLoS ONE 6: e25454. doi: 10.1371/journal.pone.0025454 Editor: Carlo Gaetano, Istituto dell Dermopatico � �I mmacolata, Italy 17th Re u May 2011; Accepted 5th September 2011; Ver published 27th September 2011 Copyright: 2011 _ Song et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which uneingeschr Distribution of spaces permitted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The study was supported by the Natural Science Foundation of China, the Program for New Century Excellent Talents in University of Science and Technology Department as th Guangdong Province, China, the Ministry of Education funded by China 890, Fund No. 200 805 580 047 and No. 20100171110080) basic research for the central university Ten. F Sponsors played no R In the study design, data collection and analysis, decision to Ver Publication or preparation of this manuscript.
Conflicts of interest: The authors have explained rt that no competing interests exist. * E-mail: junli99 gmail. The authors contributed equally S to this work. Response to DNA Sch The introduction, a complex signal transduction, induce in response to DNA-Sch By the initiation of DNA repair or apoptosis. Amount of evidence has shown that defects in a gene related to DDR, responsible for signal transduction of the discovery of bulk products to, and the repair of double strand breaks are entered could Dinner chromosome breaks, fusions have, and resettlement, the closing Lich to tumorigenesis was. For example, in connection GDR