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@article{1314701, author = {Thorenoor, Nithyananda and Vychytilová, Petra and Hombach, Sonja and Mlčochová, Jitka and Kretz, Markus and Svoboda, Marek and Slabý, Ondřej}, article_location = {Albany}, article_number = {1}, doi = {http://dx.doi.org/10.18632/oncotarget.5807}, keywords = {long non-coding RNA; ZFAS1; colorectal cancer}, language = {eng}, issn = {1949-2553}, journal = {Oncotarget}, title = {Long non-coding RNA ZFAS1 interacts with CDK1 and is involved in p53-dependent cell cycle control and apoptosis in colorectal cancer}, url = {http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=5807&path[]=19793}, volume = {7}, year = {2016} }
TY - JOUR ID - 1314701 AU - Thorenoor, Nithyananda - Vychytilová, Petra - Hombach, Sonja - Mlčochová, Jitka - Kretz, Markus - Svoboda, Marek - Slabý, Ondřej PY - 2016 TI - Long non-coding RNA ZFAS1 interacts with CDK1 and is involved in p53-dependent cell cycle control and apoptosis in colorectal cancer JF - Oncotarget VL - 7 IS - 1 SP - 622-637 EP - 622-637 PB - Impact Journals SN - 19492553 KW - long non-coding RNA KW - ZFAS1 KW - colorectal cancer UR - http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=5807&path[]=19793 L2 - http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=5807&path[]=19793 N2 - We determined expression of 83 long non-coding RNAs (lncRNAs) and identified ZFAS1 to be significantly up-regulated in colorectal cancer (CRC) tissue. In cohort of 119 CRC patients we observed that 111 cases displayed at least two-times higher expression of ZFAS1 in CRC compared to paired normal colorectal tissue (P < 0.0001). By use of CRC cell lines (HCT116-plus, HCT116-minus and DLD-1) we showed, that ZFAS1 silencing decreases proliferation through G1 arrest of cell cycle, and also tumorigenicity of CRC cells. We identified Cyclin-dependent kinase 1 (CDK1) as interacting partner of ZFAS1 by pull-down experiment and RNA immunoprecipitation. Further, we have predicted by bioinformatics approach ZFAS1 to sponge miR-590-3p, which was proved to target CDK1. Levels of CDK1 were not affected by ZFAS1 silencing, but cyclin B1 was decreased in both cell lines. We observed significant increase in p53 levels and PARP cleavage in CRC cell lines after ZFAS1 silencing indicating increase in apoptosis. Our data suggest that ZFAS1 may function as oncogene in CRC by two main actions: (i) via destabilization of p53 and through (ii) interaction with CDK1/cyclin B1 complex leading to cell cycle progression and inhibition of apoptosis. However, molecular mechanisms behind these interactions have to be further clarified. ER -
THORENOOR, Nithyananda, Petra VYCHYTILOVÁ, Sonja HOMBACH, Jitka MLČOCHOVÁ, Markus KRETZ, Marek SVOBODA and Ondřej SLABÝ. Long non-coding RNA ZFAS1 interacts with CDK1 and is involved in p53-dependent cell cycle control and apoptosis in colorectal cancer. \textit{Oncotarget}. Albany: Impact Journals, 2016, vol.~7, No~1, p.~622-637. ISSN~1949-2553. Available from: https://dx.doi.org/10.18632/oncotarget.5807.
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