PMID- 31846834
OWN - NLM
STAT- MEDLINE
DCOM- 20210526
LR  - 20210607
IS  - 1476-5586 (Electronic)
IS  - 1522-8002 (Print)
IS  - 1476-5586 (Linking)
VI  - 22
IP  - 2
DP  - 2020 Feb
TI  - Long interspersed element-1 ribonucleoprotein particles protect telomeric ends in 
      alternative lengthening of telomeres dependent cells.
PG  - 61-75
LID - S1476-5586(19)30296-9 [pii]
LID - 10.1016/j.neo.2019.11.002 [doi]
AB  - Malignant cells ensure telomere maintenance by the alternative lengthening of 
      telomeres (ALT) in the absence of telomerase activity (TA). The retrotransposons 
      "long interspersed nuclear element-1" (LINE-1, L1) are expressed in malignant 
      cells and are primarily known to contribute to complex karyotypes. Here we 
      demonstrate that LINE-1 ribonucleoprotein particles (L1-RNPs) expression is 
      significantly higher in ALT(+)- versus in TA(+)-human glioma. Analyzing a role of 
      L1-RNP in ALT, we show that L1-RNPs bind to telomeric repeat containing RNA 
      (TERRA), which is critical for telomere stabilization and which is overexpressed 
      in ALT(+) cells. In turn, L1-RNP knockdown (KD) abrogated the nuclear retention 
      of TERRA, resulted in increased telomeric DNA damage, decreased cell growth and 
      reduced expression of ALT characteristics such as c-circles and PML-bodies. 
      L1-RNP KD also decreased the expression of Shelterin- and the ALT-regulating 
      protein Topoisomerase IIIalpha (TopoIIIalpha) indicating a more general role of L1-RNPs 
      in supporting telomeric integrity in ALT. Our findings suggest an impact of 
      L1-RNP on telomere stability in ALT(+) dependent tumor cells. As L1-RNPs are 
      rarely expressed in normal adult human tissue those elements might serve as a 
      novel target for tumor ablative therapy.
CI  - Copyright (c) 2019 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Aschacher, Thomas
AU  - Aschacher T
AD  - Cardiac Surgery Research Laboratory, Department of Surgery, Medical University of 
      Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
FAU - Wolf, Brigitte
AU  - Wolf B
AD  - Surgical Research Laboratories, Department of Surgery, Medical University of 
      Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
FAU - Aschacher, Olivia
AU  - Aschacher O
AD  - Department of Plastic and Reconstructive Surgery, Department of Surgery, Medical 
      University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
FAU - Enzmann, Florian
AU  - Enzmann F
AD  - Department of Vascular and Endovascular Surgery, Paracelsus Medical University 
      Salzburg, Muellner Hauptstrasse 48, 5020 Salzburg, Austria.
FAU - Laszlo, Viktoria
AU  - Laszlo V
AD  - Surgical Research Laboratories, Department of Surgery, Medical University of 
      Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
FAU - Messner, Barbara
AU  - Messner B
AD  - Cardiac Surgery Research Laboratory, Department of Surgery, Medical University of 
      Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
FAU - Turkcan, Adrian
AU  - Turkcan A
AD  - Surgical Research Laboratories, Department of Surgery, Medical University of 
      Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
FAU - Weis, Serge
AU  - Weis S
AD  - Division of Neuropathology, Neuromed Campus, Kepler University Hospital, 4020 
      Linz, Austria.
FAU - Spiegl-Kreinecker, Sabine
AU  - Spiegl-Kreinecker S
AD  - University Clinic for Neurosurgery, Neuromed Campus, Kepler University Hospital, 
      Johannes Kepler University, Linz, Austria.
FAU - Holzmann, Klaus
AU  - Holzmann K
AD  - Department of Cancer Research, Borschkegasse 8a, 1090 Vienna, Austria; 
      Comprehensive Cancer Centre, Medical University of Vienna, Austria.
FAU - Laufer, Gunther
AU  - Laufer G
AD  - Cardiac Surgery Research Laboratory, Department of Surgery, Medical University of 
      Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
FAU - Ehrlich, Marek
AU  - Ehrlich M
AD  - Cardiac Surgery Research Laboratory, Department of Surgery, Medical University of 
      Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
FAU - Bergmann, Michael
AU  - Bergmann M
AD  - Surgical Research Laboratories, Department of Surgery, Medical University of 
      Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria; Comprehensive Cancer 
      Centre, Medical University of Vienna, Austria. Electronic address: 
      michael.bergmann@meduniwien.ac.at.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191214
PL  - United States
TA  - Neoplasia
JT  - Neoplasia (New York, N.Y.)
JID - 100886622
RN  - 0 (DMRT2 protein, human)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Ribonucleoproteins)
RN  - 0 (Transcription Factors)
RN  - EC 5.6.2.2 (TOP3A protein, human)
RN  - EC 5.99.1.2 (DNA Topoisomerases, Type I)
SB  - IM
MH  - Cell Line, Tumor
MH  - DNA Damage/genetics
MH  - DNA Topoisomerases, Type I/*genetics
MH  - DNA-Binding Proteins/*genetics
MH  - Glioma/*genetics/pathology
MH  - Humans
MH  - Long Interspersed Nucleotide Elements/genetics
MH  - Ribonucleoproteins/genetics
MH  - Telomere/*genetics
MH  - Telomere Homeostasis/genetics
MH  - Transcription Factors/*genetics
PMC - PMC6920197
OTO - NOTNLM
OT  - Alternative lengthening of telomeres
OT  - DNA damage response
OT  - LINE-1
OT  - TERRA
OT  - Telomere
EDAT- 2019/12/18 06:00
MHDA- 2021/05/27 06:00
PMCR- 2019/12/14
CRDT- 2019/12/18 06:00
PHST- 2019/06/28 00:00 [received]
PHST- 2019/11/13 00:00 [revised]
PHST- 2019/11/14 00:00 [accepted]
PHST- 2019/12/18 06:00 [pubmed]
PHST- 2021/05/27 06:00 [medline]
PHST- 2019/12/18 06:00 [entrez]
PHST- 2019/12/14 00:00 [pmc-release]
AID - S1476-5586(19)30296-9 [pii]
AID - 10.1016/j.neo.2019.11.002 [doi]
PST - ppublish
SO  - Neoplasia. 2020 Feb;22(2):61-75. doi: 10.1016/j.neo.2019.11.002. Epub 2019 Dec 
      14.