Genome-wide microarray-based analysis of miRNAs expression in patients with acute-on-chronic liver failure.
BACKGROUND
Acute-on-chronic liver failure (ACLF) is a severe clinical syndrome that may cause a high mortality. However, the mechanism is still not clear. Characterization of the microRNA (miRNA) profiles in ACLF patients may provide new clues to the pathogenesis and management of this syndrome.


METHODS
Genome-wide microarray was performed to compare the different miRNA expression profiles in peripheral blood mononuclear cells of a pair of monozygotic twins, an ACLF patient and an HBV asymptomatic carrier (AsC). The case-control miRNA profiles were compared and confirmed by quantitative reverse transcription-polymerase chain reaction in 104 ACLF patients and 96 AsCs. A combined computational prediction algorithm was used to predict the potential target genes.


RESULTS
Forty-five miRNAs were increased and eight miRNAs were decreased in the ACLF group. The expressions of hsa-let-7a and hsa-miR-16 were increased by 8.58- and 8.63-fold in ACLF patients compared with that in AsCs, respectively (P<0.001). CARD8, BCL2, IL1RAPL1, LTB, FZD10 and EDA were identified as the target genes of hsa-miR-16; MAP4K3, OPRM1, IGF2BP1 and CERCAM were verified as the target genes of hsa-let-7a.


CONCLUSIONS
Our results showed that there is a close relationship between specific miRNAs of peripheral blood mononuclear cells and ACLF. hsa-miR-16 and hsa-let-7a may contribute to the development of ACLF.
Institute of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. wym417@ 163.com.
Wen
W
Chen
Ze-Hui
ZH
Yan
Yu-Ming
YM
Wang
Bao-Yan
BY
Xu
Guo-Hong
GH
Deng
D065290:Acute-On-Chronic Liver Failure / Q000235:genetics* / Q000378:metabolism*; D000328:Adult; D000465:Algorithms; D002353:Carrier State; D016022:Case-Control Studies; D005260:Female; D055106:Genome-Wide Association Study; D006526:Hepatitis C; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D059467:Transcriptome; D014430:Twins, Monozygotic / Q000235:genetics
C505362:MIRN16 microRNA, human; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human