A novel function of microRNA let-7d in regulation of galectin-3 expression in attention deficit hyperactivity disorder rat brain.
In this study we investigated the locomotor activity and non-selective attention in spontaneously hypertensive rats (SHR) with control Wistar-Kyoto (WKY) rats, which were employed as an attention deficit hyperactivity disorder (ADHD) model. In open-field test and làt maze, SHR rats were found to be much more spontaneously active than WKY rats. As compared with WKY rats, a lower level of galectin-3 was observed in SHR brain prefrontal cortex (PFC), which was the major affected brain area of ADHD. Through miRNA microarray screening, rno-let-7d was noted to be solely upregulated in SHR PFC. Interestingly, rno-let-7d had a binding site at galectin-3 mRNA and was shown to regulate galectin-3 3' untranslated region (UTR) directly. Mutation of galectin-3 3'UTR by one nucleotide of the seed sequence prevented rno-let-7d regulation of the 3' UTR completely. Although rno-let-7d did not directly regulate tyrosine hydroxylase (TH) 3'UTR, the level of galectin-3 was important for cAMP response element binding protein, the major transcript factor for TH gene. Either overexpression or downexpression of galectin-3 could result in modulation of TH expression in both PC12H and PC12L cells. In conclusion, our data suggested a novel function of rno-let-7d in regulation of galectin-3 and in ADHD development. Rno-let-7d, which is increased in the PFC of SHR brain, negatively regulated galectin-3, which is coupled with TH expression regulation.
Wu
Lihui
L
Department of Children's Health Care, Yu Ying Children's Hospital, Wenzhou Medical College, Cha Shan College Zone, Wenzhou, China. lhwu@wzmc.net
Zhao
Qianlei
Q
Zhu
Xuchao
X
Peng
Min
M
Jia
Chenyou
C
Wu
Wei
W
Zheng
Jing
J
Wu
Xing Zhong
XZ
D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D050882:CREB-Binding Protein / Q000378:metabolism; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D008124:Locomotion / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D046228:Microarray Analysis / Q000379:methods; D016716:PC12 Cells; D017397:Prefrontal Cortex / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014162:Transfection / Q000379:methods; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D037502:Galectin 3; C548145:MIRNLET7 microRNA, rat; D035683:MicroRNAs; D012333:RNA, Messenger; D014446:Tyrosine 3-Monooxygenase; D050882:CREB-Binding Protein