title: DNA methyltransferase 3, a target of microRNA-29c, contributes to neuronal proliferation by regulating the expression of brain-derived neurotrophic factor.
abstract: 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.
authors: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors: Guoshuai
authors: G
authors: Yang
authors: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors: Yanmin
authors: Y
authors: Song
authors: Department of Neurology, Haikou People's Hospital, Haikou, Hainan 570208, P.R. China.
authors: Xiaoyan
authors: X
authors: Zhou
authors: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors: Yidong
authors: Y
authors: Deng
authors: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors: Tao
authors: T
authors: Liu
authors: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors: Guohu
authors: G
authors: Weng
authors: Department of Neurology, Haikou People's Hospital, Haikou, Hainan 570208, P.R. China.
authors: Dan
authors: D
authors: Yu
authors: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors: Suyue
authors: S
authors: Pan
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001374:Azacitidine / Q000008:administration & dosage; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000134:cerebrospinal fluid; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000134:cerebrospinal fluid; D019175:DNA Methylation / Q000235:genetics; D000090205:DNA Methyltransferase 3A; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000134:cerebrospinal fluid / Q000235:genetics*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture; D051381:Rats; D015398:Signal Transduction
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C000717967:DNMT3A protein, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; C579455:BDNF protein, human; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D001374:Azacitidine