PMID- 25815896
OWN - NLM
STAT- MEDLINE
DCOM- 20160115
LR  - 20211203
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Linking)
VI  - 12
IP  - 1
DP  - 2015 Jul
TI  - DNA methyltransferase 3, a target of microRNA-29c, contributes to neuronal 
      proliferation by regulating the expression of brain-derived neurotrophic factor.
PG  - 1435-42
LID - 10.3892/mmr.2015.3531 [doi]
AB  - Alzheimer's disease (AD), the most common form of dementia in the aged 
      population, presents an increasing clinical challenge in terms of diagnosis and 
      treatment. Neurodegeneration is one of the hallmarks of AD, which consequently 
      induces cognitive impairment. Brain-derived neurotrophic factor (BDNF), a 
      neuroprotective factor, has been implicated in neuronal survival and 
      proliferation. The epigenetic mechanism of BDNF methylation may be responsible 
      for the reduced expression of BDNF in patients with AD. DNA methyltransferase may 
      contribute to the methylation of BDNF, which is involved in neuroprotection in 
      AD. In addition, epigenetic modifications, including a combination of microRNAs 
      (miRNAs/miRs) and DNA methylation, have been suggested as regulatory mechanisms 
      in the control of neuronal survival. In the present study, the expression of 
      miR-29c was determined in the cerebrospinal fluid (CSF) of patients with AD and 
      of healthy control individuals. A marked decrease in the expression of miR-29c 
      was observed in the AD group compared with the normal control group, accompanied 
      by a decreased in the expression of BDNF. Additionally, a significant increase in 
      the expression of DNA methyltransferase 3 (DNMT3) was observed in the CSF from 
      the patients with AD. Correlation analysis revealed that the expression of 
      miR-29c was positively correlated with BDNF and negatively correlated with DNMT3 
      protein in the CSF of patients with AD. In addition, the regulatory association 
      between miR-29c, DNMT3 and BDNF were also examined in vitro. It was demonstrated 
      that miR-29c directly targeted DNMT3 and contributed to neuronal proliferation by 
      regulating the expression of BDNF, at least partially, through enhancing the 
      activity of the tyrosine receptor kinase B/extracellular signal-regulated kinase 
      signaling pathway. In conclusion, the present study suggested that miR-29c may be 
      a promising potential therapeutic target in the treatment of AD.
FAU - Yang, Guoshuai
AU  - Yang G
AD  - Department of Neurology, Nanfang Hospital, Southern Medical University, 
      Guangzhou, Guangdong 510515, P.R. China.
FAU - Song, Yanmin
AU  - Song Y
AD  - Department of Neurology, Xiangya Hospital, Central South University, Changsha, 
      Hunan 410008, P.R. China.
FAU - Zhou, Xiaoyan
AU  - Zhou X
AD  - Department of Neurology, Haikou People's Hospital, Haikou, Hainan 570208, P.R. 
      China.
FAU - Deng, Yidong
AU  - Deng Y
AD  - Department of Neurology, Nanfang Hospital, Southern Medical University, 
      Guangzhou, Guangdong 510515, P.R. China.
FAU - Liu, Tao
AU  - Liu T
AD  - Department of Neurology, Nanfang Hospital, Southern Medical University, 
      Guangzhou, Guangdong 510515, P.R. China.
FAU - Weng, Guohu
AU  - Weng G
AD  - Department of Neurology, Nanfang Hospital, Southern Medical University, 
      Guangzhou, Guangdong 510515, P.R. China.
FAU - Yu, Dan
AU  - Yu D
AD  - Department of Neurology, Haikou People's Hospital, Haikou, Hainan 570208, P.R. 
      China.
FAU - Pan, Suyue
AU  - Pan S
AD  - Department of Neurology, Nanfang Hospital, Southern Medical University, 
      Guangzhou, Guangdong 510515, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20150323
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (DNMT3A protein, human)
RN  - 0 (MIRN29a microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases)
RN  - EC 2.1.1.37 (DNA Methyltransferase 3A)
RN  - M801H13NRU (Azacitidine)
SB  - IM
MH  - Alzheimer Disease/cerebrospinal fluid/*genetics/pathology
MH  - Animals
MH  - Apoptosis/genetics
MH  - Azacitidine/administration & dosage
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis/cerebrospinal fluid
MH  - Cell Proliferation/genetics
MH  - Cell Survival/genetics
MH  - DNA (Cytosine-5-)-Methyltransferases/antagonists & 
      inhibitors/*biosynthesis/cerebrospinal fluid
MH  - DNA Methylation/genetics
MH  - DNA Methyltransferase 3A
MH  - Gene Expression Regulation
MH  - Humans
MH  - MicroRNAs/cerebrospinal fluid/*genetics
MH  - Neurons/metabolism/pathology
MH  - Primary Cell Culture
MH  - Rats
MH  - Signal Transduction
EDAT- 2015/03/31 06:00
MHDA- 2016/01/16 06:00
CRDT- 2015/03/28 06:00
PHST- 2014/06/12 00:00 [received]
PHST- 2015/02/24 00:00 [accepted]
PHST- 2015/03/28 06:00 [entrez]
PHST- 2015/03/31 06:00 [pubmed]
PHST- 2016/01/16 06:00 [medline]
AID - 10.3892/mmr.2015.3531 [doi]
PST - ppublish
SO  - Mol Med Rep. 2015 Jul;12(1):1435-42. doi: 10.3892/mmr.2015.3531. Epub 2015 Mar 
      23.