Human vtRNA1-1 Levels Modulate Signaling Pathways and Regulate Apoptosis in Human Cancer Cells

被引:21
作者
Bracher, Lisamaria [1 ,2 ]
Ferro, Iolanda [1 ]
Pulido-Quetglas, Carlos [2 ,3 ,4 ,5 ]
Ruepp, Marc-David [1 ,6 ]
Johnson, Rory [3 ,4 ,5 ]
Polacek, Norbert [1 ]
机构
[1] Univ Bern, Dept Chem & Biochem, CH-3012 Bern, Switzerland
[2] Univ Bern, Grad Sch Cellular & Biomed Sci, CH-3012 Bern, Switzerland
[3] Univ Hosp, Dept Med Oncol, Inselspital, CH-3010 Bern, Switzerland
[4] Univ Bern, CH-3010 Bern, Switzerland
[5] Univ Bern, Dept BioMed Res, CH-3008 Bern, Switzerland
[6] Kings Coll London, Inst Psychiat Psychol & Neurosci, Maurice Wohl Clin Neurosci Inst, United Kingdom Dementia Res Inst, London SE5 9NU, England
基金
英国医学研究理事会; 瑞士国家科学基金会;
关键词
non-coding RNA; vault RNA; apoptosis; signaling; MAJOR VAULT PROTEIN; NONCODING RNA; MULTIDRUG-RESISTANCE; PHOSPHORYLATION; KINASE; PTEN; LOCALIZATION; INACTIVATION; PURIFICATION; MITOXANTRONE;
D O I
10.3390/biom10040614
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Regulatory non-protein coding RNAs perform a remarkable variety of complex biological functions. Previously, we demonstrated a role of the human non-coding vault RNA1-1 (vtRNA1-1) in inhibiting intrinsic and extrinsic apoptosis in several cancer cell lines. Yet on the molecular level, the function of the vtRNA1-1 is still not fully clear. Here, we created HeLa knock-out cell lines revealing that prolonged starvation triggers elevated levels of apoptosis in the absence of vtRNA1-1 but not in vtRNA1-3 knock-out cells. Next-generation deep sequencing of the mRNome identified the PI3K/Akt pathway and the ERK1/2 MAPK cascade, two prominent signaling axes, to be misregulated in the absence of vtRNA1-1 during starvation-mediated cell death conditions. Expression of vtRNA1-1 mutants identified a short stretch of 24 nucleotides of the vtRNA1-1 central domain as being essential for successful maintenance of apoptosis resistance. This study describes a cell signaling-dependent contribution of the human vtRNA1-1 to starvation-induced programmed cell death.
引用
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页数:20
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