Long non-coding RNA ZFAS1 interacts with CDK1 and is involved in p53-dependent cell cycle control and apoptosis in colorectal cancer

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. 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.

Basic information

• Original name: Long non-coding RNA ZFAS1 interacts with CDK1 and is involved in p53-dependent cell cycle control and apoptosis in colorectal cancer
• Authors: THORENOOR, Nithyananda (356 India, belonging to the institution), Petra VYCHYTILOVÁ (203 Czech Republic, belonging to the institution), Sonja HOMBACH (276 Germany), Jitka MLČOCHOVÁ (203 Czech Republic, belonging to the institution), Markus KRETZ (276 Germany), Marek SVOBODA (203 Czech Republic) and Ondřej SLABÝ (203 Czech Republic, guarantor, belonging to the institution).
• Edition: Oncotarget, Albany, Impact Journals, 2016, 1949-2553.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 30200 3.2 Clinical medicine
• Country of publisher: United States of America
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 5.168
• RIV identification code: RIV/00216224:14740/16:00088833
• Organization unit: Central European Institute of Technology
• Doi: http://dx.doi.org/10.18632/oncotarget.5807
• UT WoS: 000369950300047
• Keywords (in Czech): dlouhé nekódující RNA; ZFAS1; kolorektální karcinom
• Keywords in English: long non-coding RNA; ZFAS1; colorectal cancer
• Tags: rivok
• Tags: International impact, Reviewed

Abstract

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.

Links

• ED1.1.00/02.0068, research and development project: Name: CEITEC - central european institute of technology
• EE2.3.30.0037, research and development project: Name: Zaměstnáním nejlepších mladých vědců k rozvoji mezinárodní spolupráce
• NT13549, research and development project: Name: Vytvoření diagnostické sady cirkulujících mikroRNA pro neinvazivní časnou diagnostiku a sledování pacientů s kolorektálním karcinomem
• 90004, large research infrastructures: Name: BBMRI-CZ