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Chunk #35 — Discussion

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Up-regulation of microRNAs in brain of human alcoholics.
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In addition, genes involved in lipid metabolism (PLP1,SPTLC2,SCD,PIK3C2B,SGMS1,FAR1,PLCL1,TEX2,ELOVL5,ELOVL4,LA SS2,ELOVL7,OSBPL11), ubiquitination (UFSP2,BIRC6,FBXL3,USP31), and cell death (SGK1,PLP1,CDKN1B,SPG20,RYBP,BIRC6,RIPK2,SGMS1,DIDO1,SPAST,TP53I NP1,TGFB2) (see Table 5) are differentially expressed and over-represented in our genome-wide mRNA profiling study as well as over-represented as predicted targets of miRNA changing expression in the same samples. Furthermore, out of a list of 27 genes previously identified in other alcohol studies using autopsy human brain (Flatscher-Bader et al., 2005; Lavoie and Butterworth, 1995; Lewohl et al., 2000; Liu et al., 2006; Mayfield et al., 2002; Sokolov et al., 2003), about half of them (13/27) were also identified as potential targets of differentially expressed miRNAs. These included: Calpain 3 (p94) (CAPN3); Lysosomal-associated membrane protein 2 (LAMP2); EGF-like repeats and discoidin I-like domains 3 (EDIL3); sparc/osteonectin, cwcv and kazal-like domains proteoglycan (testican) 1 (SPOCK1); TIMP metallopeptidase inhibitor 2 (TIMP2), SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 5 (SMARCA5); Calnexin (CANX); Unc-51-like kinase 2 (ULK2); proteolipid protein 1 (Pelizaeus-Merzbacher disease, spastic paraplegia 2, uncomplicated) (PLP1); 2′,3′-cyclic nucleotide 3′ phosphodiesterase (CNP); transketolase (Wernicke-Korsakoff syndrome) (TKT); stearoyl-CoA desaturase (delta-9-desaturase) (SCD); and acidic (leucine-rich) nuclear phosphoprotein 32 family, member E (AMP32E).