PMID- 26916825
OWN - NLM
STAT- MEDLINE
DCOM- 20160722
LR  - 20160316
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 150
DP  - 2016 Apr 1
TI  - Expression of zTOR-associated microRNAs in zebrafish embryo treated with 
      rapamycin.
PG  - 67-75
LID - S0024-3205(16)30126-6 [pii]
LID - 10.1016/j.lfs.2016.02.076 [doi]
AB  - AIMS: MicroRNAs (miRNAs) are vital in modulating lifespan and various biological 
      processes including vascular function. The pivotal roles of mammalian target of 
      rapamycin (mTOR) in regulating senescence and angiogenesis have been extensively 
      described. However, the roles of its orthologue, zebrafish target of rapamycin 
      (zTOR) in senescence and angiogenesis remain to be unravelled. In the present 
      study, we aimed to investigate the role of zTOR and identify miRNAs associated 
      with senescence and angiogenesis. MAIN METHODS: Zebrafish embryos were treated 
      with rapamycin and the inhibition of zTOR and its downstream proteins were 
      validated by immunoblotting. Following the treatment, melanocyte density was 
      quantitated, and senescence and angiogenic responses were determined by 
      senescence-associated beta-galactosidase (SA-beta-gal) and endogenous alkaline 
      phosphatase (ALP) staining, respectively. Relative expression of microRNAs were 
      determined by quantitative RT-PCR. KEY FINDINGS: Rapamycin (400 nM) suppressed 
      zTOR pathway by down-regulating the phosphorylation of zTOR-associated proteins 
      such as P70S6K and S6K at both 4h post-fertilisation (hpf) and 8hpf while 4E-BP1 
      was only down-regulated at 8hpf when compared to their respective vehicle 
      controls. Treatment with rapamycin also resulted in significant suppression of 
      melanocyte development and senescence-associated beta-galactosidase (SA-beta-gal) 
      activity, and perturbed the development of intersegmental vessels (ISVs) of 
      zebrafish embryos. In addition, the expressions of dre-miR-9-5p and -3p, 
      dre-miR-25-3p and dre-miR-124-3p were significantly up-regulated in embryos 
      treated with rapamycin from 4hpf. SIGNIFICANCE: Our findings suggest the 
      involvement of zTOR in embryonic senescence and angiogenesis which could be 
      potentially mediated by selected miRNAs.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Khor, Eng-Soon
AU  - Khor ES
AD  - Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 
      Kuala Lumpur, Malaysia. Electronic address: darren_khor@hotmail.my.
FAU - Noor, Suzita Mohd
AU  - Noor SM
AD  - Department of Biomedical Science, Faculty of Medicine, University of Malaya, 
      50603 Kuala Lumpur, Malaysia. Electronic address: suzita@um.edu.my.
FAU - Wong, Pooi-Fong
AU  - Wong PF
AD  - Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 
      Kuala Lumpur, Malaysia. Electronic address: wongpf@um.edu.my.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160223
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (MicroRNAs)
RN  - 0 (Torc1 protein complex, zebrafish)
RN  - 0 (Transcription Factors)
RN  - 0 (Zebrafish Proteins)
RN  - EC 3.1.3.1 (Alkaline Phosphatase)
RN  - EC 3.2.1.23 (beta-Galactosidase)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Aging/genetics
MH  - Alkaline Phosphatase/metabolism
MH  - Animals
MH  - Down-Regulation/drug effects
MH  - Embryo, Nonmammalian
MH  - Melanocytes/drug effects
MH  - MicroRNAs/*biosynthesis/drug effects/genetics
MH  - Neovascularization, Physiologic/genetics
MH  - Sirolimus/*pharmacology
MH  - Transcription Factors/*biosynthesis/genetics
MH  - Zebrafish
MH  - Zebrafish Proteins/*biosynthesis/genetics
MH  - beta-Galactosidase/biosynthesis/genetics
OTO - NOTNLM
OT  - Aging
OT  - Embryonic development
OT  - Mammalian target of rapamycin
OT  - Zebrafish
EDAT- 2016/02/27 06:00
MHDA- 2016/07/23 06:00
CRDT- 2016/02/27 06:00
PHST- 2015/11/24 00:00 [received]
PHST- 2016/02/17 00:00 [revised]
PHST- 2016/02/21 00:00 [accepted]
PHST- 2016/02/27 06:00 [entrez]
PHST- 2016/02/27 06:00 [pubmed]
PHST- 2016/07/23 06:00 [medline]
AID - S0024-3205(16)30126-6 [pii]
AID - 10.1016/j.lfs.2016.02.076 [doi]
PST - ppublish
SO  - Life Sci. 2016 Apr 1;150:67-75. doi: 10.1016/j.lfs.2016.02.076. Epub 2016 Feb 23.