الفهرس 
MICRORNA
MicroRNA and Different Disease StatesOnly 14 pages are availabe for public view
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Abstract
Hepatitis C virus infection is a major cause of chronic
hepatitis, liver cirrhosis and hepatocellular carcinoma
worldwide. It has been estimated that 180 million people are
infected worldwide.
MicroRNAs are small non-coding RNAs of 19–24
nucleotides in length that regulate gene expression by posttranscriptional
mechanism. MiR-122 expression is enriched in
the liver, accounting for approximately 70 % of the total
miRNA population in normal adult hepatocytes. It plays a
crucial role in the HCV infection.
The aim of this study was to determine gene expression
of miR-122 in both hepatic tissue and peripheral blood of
chronic HCV infected Egyptian patients and to correlate the
level of expression with the serum HCV load.
All subjects enrolled in the study were recruited from
Ain Shams University Specialized Hospital, Transplantation
Unit, and the laboratory work was conducted in Clinical
Pathology Department, Immunology Unit Ain Shams
University Hospital.
The study included 20 patients diagnosed as CHC
(group I) and 10 healthy controls (group II). group (I) was further subdivided according to the results of the last HCV RTPCR
into two groups:-
group IA: Including 17 patients with HCV-PCR positive.
group IB: Including 3 patients with HCV-PCR negative.
All individuals included were subjected to measurement
of AST, ALT, ALP, ALB, AFP and HCV load. The study
showed high statistical significant difference (P<0.001)
between CHC patients and control group regarding ALT, AST,
ALP and AFP being higher in the former group. On the other
hand, serum level of ALB showed a high statistical significant
difference (P<0.001) between both groups being decreased in
CHC patients.
Similarly, there was statistical significant increase
(P<0.05) of serum AST level, and decrease of serum AFP in
group IA when compared to group IB.
Detection and relative quantification of miR-122
expression levels, was performed on 30 peripheral blood
samples using RT- PCR. Regarding miR-122 expression level,
a statistically significant difference was found between CHC
patients when compared to control group (P <0.001).
Similarly, statistical significant difference of both miR-
122 expression levels in the peripheral blood or hepatic tissue
being higher in-group IA when compared to group IB (P<0.001). On the other hand, there was no significant
difference between group IB and group II as regard peripheral
blood miR-122 gene expression.
Regarding the correlation between miR-122 expression
levels in both peripheral blood and liver tissue and each of ALT
and AST, the study showed a significant positive correlation.
On the other hand, there was statistical significant negative
correlation with AFP level in group I and group IA.
In conclusion, our results demonstrated a significantly
higher expression of miR-122 in adult Egyptian CHC patients
compared to controls and a strong association of miR-122 with
hepatocyte necroinflammation markers (AST, ALT) indicating
that it may play an important role in activ state of HCV and
introduces it as a potential predictor of disease progression.
These findings lead us to conclude that HCV infection results
in modulation of miR-122 gene expression, a finding that has
drawn our attention to the possible role of miR-122 in viral
confrontation and clearance.
However, the biological functions of these miRNAs
require further investigation to elucidate if serum miR-122 may
serve as an interesting biomarker for early hepatic
inflammation responses or other pathological process in HCV
patients. We also conclude that elevated serum miR-122 levels
may require further understanding of the role of liver injury and
an s yet undetermined additional mechanism of active synthesis
of miR-122 that is most evident during chronic HCV infection,
and accounts for the high levels of circulating miR-122
observed. Further understanding of miR function may indicate
whether induced levels are secondary to an intrinsic hepatocyte
response or represent a mechanism unique to HCV.
Understanding miR-122 elevations in the hepatitis C setting
might lead to new antiviral strategies.