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

J 2016

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 et. al.

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30200 3.2 Clinical medicine

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

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

Abstract

V originále

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

Citovat

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.

@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.

Detailed Information on Publication Record