microRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder

被引:420
作者
Perkins, Diana O.
Jeffries, Clark D.
Jarskog, L. Fredrik
Thomson, J. Michael
Woods, Keith
Newman, Martin A.
Parker, Joel S.
Jin, Jianping
Hammond, Scott M.
机构
[1] Univ N Carolina, Sch Pharm, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA
[3] Univ N Carolina, Renaissance Comp Inst, Chapel Hill, NC 27599 USA
[4] Univ N Carolina, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA
[5] Constella Grp LLC, Meridian Pkwy, Durham, NC 27713 USA
[6] Univ N Carolina, Dept Biol Mol, Chapel Hill, NC 27599 USA
关键词
D O I
10.1186/gb-2007-8-2-r27
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Background: microRNAs (miRNAs) are small, noncoding RNA molecules that are now thought to regulate the expression of many mRNAs. They have been implicated in the etiology of a variety of complex diseases, including Tourette's syndrome, Fragile x syndrome, and several types of cancer. Results: We hypothesized that schizophrenia might be associated with altered miRNA profiles. To investigate this possibility we compared the expression of 264 human miRNAs from postmortem prefrontal cortex tissue of individuals with schizophrenia (n = 13) or schizoaffective disorder (n = 2) to tissue of 21 psychiatrically unaffected individuals using a custom miRNA microarray. Allowing a 5% false discovery rate, we found that 16 miRNAs were differentially expressed in prefrontal cortex of patient subjects, with 15 expressed at lower levels (fold change 0.63 to 0.89) and 1 at a higher level (fold change 1.77) than in the psychiatrically unaffected comparison subjects. The expression levels of 12 selected miRNAs were also determined by quantitative RT-PCR in our lab. For the eight miRNAs distinguished by being expressed at lower microarray levels in schizophrenia samples versus comparison samples, seven were also expressed at lower levels with quantitative RT-PCR. Conclusion: This study is the first to find altered miRNA profiles in postmortem prefrontal cortex from schizophrenia patients.
引用
收藏
页数:11
相关论文
共 53 条
[21]   RNA and microRNAs in fragile X mental retardation [J].
Jin, P ;
Alisch, RS ;
Warren, ST .
NATURE CELL BIOLOGY, 2004, 6 (11) :1048-1053
[22]   The molecular genetics of the 22q11-associated schizophrenia [J].
Karayiorgou, M ;
Gogos, JA .
MOLECULAR BRAIN RESEARCH, 2004, 132 (02) :95-104
[23]   The human genome browser at UCSC [J].
Kent, WJ ;
Sugnet, CW ;
Furey, TS ;
Roskin, KM ;
Pringle, TH ;
Zahler, AM ;
Haussler, D .
GENOME RESEARCH, 2002, 12 (06) :996-1006
[24]   A microRNA array reveals extensive regulation of microRNAs during brain development [J].
Krichevsky, AM ;
King, KS ;
Donahue, CP ;
Khrapko, K ;
Kosik, KS .
RNA, 2003, 9 (10) :1274-1281
[25]   Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets [J].
Lewis, BP ;
Burge, CB ;
Bartel, DP .
CELL, 2005, 120 (01) :15-20
[26]   Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method [J].
Livak, KJ ;
Schmittgen, TD .
METHODS, 2001, 25 (04) :402-408
[27]   MicroRNA expression profiles classify human cancers [J].
Lu, J ;
Getz, G ;
Miska, EA ;
Alvarez-Saavedra, E ;
Lamb, J ;
Peck, D ;
Sweet-Cordero, A ;
Ebet, BL ;
Mak, RH ;
Ferrando, AA ;
Downing, JR ;
Jacks, T ;
Horvitz, HR ;
Golub, TR .
NATURE, 2005, 435 (7043) :834-838
[28]   Aberrant T cell differentiation in the absence of Dicer [J].
Muljo, SA ;
Ansel, KM ;
Kanellopoulou, C ;
Livingston, DM ;
Rao, A ;
Rajewsky, K .
JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 202 (02) :261-269
[29]   Visualizing phosphoinositide signalling in single neurons gets a green light [J].
Nahorski, SR ;
Young, KW ;
Challiss, RAJ ;
Nash, MS .
TRENDS IN NEUROSCIENCES, 2003, 26 (08) :444-452
[30]   RAKE and LNA-ISH reveal microRNA expression and localization in archival human brain [J].
Nelson, PT ;
Baldwin, DA ;
Kloosterman, WP ;
Kauppinen, S ;
Plasterk, RHA ;
Mourelatos, Z .
RNA, 2006, 12 (02) :187-191