PMID- 23595747
OWN - NLM
STAT- MEDLINE
DCOM- 20130617
LR  - 20220408
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 33
IP  - 16
DP  - 2013 Apr 17
TI  - The MicroRNA-17-92 cluster enhances axonal outgrowth in embryonic cortical 
      neurons.
PG  - 6885-94
LID - 10.1523/JNEUROSCI.5180-12.2013 [doi]
AB  - MicroRNAs (miRNAs) regulate dendritogenesis and plasticity. However, the 
      biological function of miRNAs in axons has not been extensively investigated. 
      Here, using rat primary cortical neurons cultured in a microfluidic chamber, we 
      found that the distal axons of the neurons expressed the miR-17-92 cluster, and 
      proteins that regulate production and activity of mature miRNAs, Dicer and 
      Argonaute 2, respectively, were present in the distal axons. Overexpression of 
      the miR-17-92 cluster in cortical neurons substantially increased axonal 
      outgrowth, whereas distal axonal attenuation of endogenous miR-19a, a key miRNA 
      of the miR-17-92 cluster, with the miRNA hairpin inhibitor suppressed axonal 
      outgrowth. Moreover, overexpression of the miR-17-92 cluster reduced phosphatase 
      and tensin homolog (PTEN) proteins and elevated phosphorylated mammalian target 
      of rapamycin (mTOR) in the distal axons. In contrast, distal axonal attenuation 
      of miR-19a increased PTEN proteins and inactivated mTOR in the axons, but did not 
      affect these protein levels in the cell bodies. Overexpression of PTEN and 
      attenuation of endogenous PTEN prevailed over the enhancement and inhibitory 
      effects of the miR-19a on axonal outgrowth, respectively. Axonal application of 
      LY294002, a phosphoinositide3-kinase inhibitor, or rapamycin, an mTOR inhibitor, 
      abolished axonal outgrowth enhanced by overexpression of the miR-17-92 cluster. 
      Collectively, these findings demonstrate that axonal alteration of miR-17-92 
      cluster expression regulates axonal outgrowth and that local modulation of PTEN 
      protein levels by miR-19a likely contributes to the axonal outgrowth.
FAU - Zhang, Yi
AU  - Zhang Y
AD  - Department of Neurology, Henry Ford Hospital, Detroit, Michigan 48202, USA.
FAU - Ueno, Yuji
AU  - Ueno Y
FAU - Liu, Xian Shuang
AU  - Liu XS
FAU - Buller, Benjamin
AU  - Buller B
FAU - Wang, Xinli
AU  - Wang X
FAU - Chopp, Michael
AU  - Chopp M
FAU - Zhang, Zheng Gang
AU  - Zhang ZG
LA  - eng
GR  - R01 AG037506/AG/NIA NIH HHS/United States
GR  - R01 NS075156/NS/NINDS NIH HHS/United States
GR  - R01 NS75156/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Small Interfering)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (Pten protein, rat)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Axons/drug effects/*physiology
MH  - Cells, Cultured
MH  - Cerebral Cortex/*cytology
MH  - Embryo, Mammalian
MH  - Glycogen Synthase Kinase 3/metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Green Fluorescent Proteins/genetics
MH  - Immunosuppressive Agents/pharmacology
MH  - MicroRNAs/genetics/*metabolism
MH  - Microfluidic Analytical Techniques
MH  - Neurons/*cytology/drug effects
MH  - PTEN Phosphohydrolase/genetics/metabolism
MH  - RNA, Small Interfering/metabolism/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Time Factors
MH  - Transfection
PMC - PMC3657758
MID - NIHMS469014
EDAT- 2013/04/19 06:00
MHDA- 2013/06/19 06:00
PMCR- 2013/10/17
CRDT- 2013/04/19 06:00
PHST- 2013/04/19 06:00 [entrez]
PHST- 2013/04/19 06:00 [pubmed]
PHST- 2013/06/19 06:00 [medline]
PHST- 2013/10/17 00:00 [pmc-release]
AID - 33/16/6885 [pii]
AID - 5180-12 [pii]
AID - 10.1523/JNEUROSCI.5180-12.2013 [doi]
PST - ppublish
SO  - J Neurosci. 2013 Apr 17;33(16):6885-94. doi: 10.1523/JNEUROSCI.5180-12.2013.