Elevated miR-33a and miR-224 in steatotic chronic hepatitis C liver biopsies.
OBJECTIVE
To assess the expression of selected microRNAs (miRNA) in hepatitis C, steatotic hepatitis C, noninfected steatotic and normal liver tissues.


METHODS
The relative expression levels of miR-21, miR-33a, miR-96, miR-122, miR-125b, miR-221 and miR-224 were determined in 76 RNA samples isolated from 18 non-steatotic and 28 steatotic chronic hepatitis C (CHC and CHC-Steatosis, respectively) cases, 18 non-infected, steatotic liver biopsies of metabolic origin (Steatosis) and 12 normal formalin-fixed paraffin-embedded liver tissues using TaqMan MicroRNA Assays. All CHC biopsy samples were obtained prior to initiating therapy. Patients' serum biochemical values, which included glucose, triglyceride, cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl-transferase (GGT), alkaline phosphatase (AP), were obtained and correlated with relative miRNA expression.


RESULTS
When compared with control non-infected liver samples, miR-122 and miR-221 levels were reduced in CHC-Steatosis (P < 0.03) and in CHC, CHC-Steatosis and Steatosis (P < 0.01). Alternatively, the expression of miR-33a and miR-224 were elevated in CHC-Steatosis and Steatosis in comparison to control tissue (P < 0.01). The levels of miR-33a and miR-224 in CHC-Steatosis (P < 0.02) and miR-224 in Steatosis (P < 0.001) were increased in comparison to CHC samples. By contrast, the expression of miR-21 did not differ statistically between diseased and normal liver samples. Levels of miR-33a correlated negatively with serum AST and AP levels in Steatosis as well as with necroinflammatory grade in CHC, whereas miR-21 correlated positively with AST in Steatosis and displayed negative correlation with triglyceride level in CHC-Steatosis. In contrast, miRNA levels were not correlated with ALT, GGT, cholesterol levels or fibrosis stage.


CONCLUSIONS
Differences in miRNA expression were observed between CHC and steatotic CHC, CHC and steatotic liver, but not between steatotic CHC and steatotic liver of metabolic origin.
Gabor Lendvai, Zsuzsa Schaff, MTA-SE Tumor Progression Research Group, Semmelweis University, 1091 Budapest, Hungary.
Gabor
G
Lendvai
Gabor Lendvai, Zsuzsa Schaff, MTA-SE Tumor Progression Research Group, Semmelweis University, 1091 Budapest, Hungary.
Katalin
K
Jármay
Gabor Lendvai, Zsuzsa Schaff, MTA-SE Tumor Progression Research Group, Semmelweis University, 1091 Budapest, Hungary.
Gizella
G
Karácsony
Gabor Lendvai, Zsuzsa Schaff, MTA-SE Tumor Progression Research Group, Semmelweis University, 1091 Budapest, Hungary.
Tünde
T
Halász
Gabor Lendvai, Zsuzsa Schaff, MTA-SE Tumor Progression Research Group, Semmelweis University, 1091 Budapest, Hungary.
Ilona
I
Kovalszky
Gabor Lendvai, Zsuzsa Schaff, MTA-SE Tumor Progression Research Group, Semmelweis University, 1091 Budapest, Hungary.
Kornélia
K
Baghy
Gabor Lendvai, Zsuzsa Schaff, MTA-SE Tumor Progression Research Group, Semmelweis University, 1091 Budapest, Hungary.
Tibor
T
Wittmann
Gabor Lendvai, Zsuzsa Schaff, MTA-SE Tumor Progression Research Group, Semmelweis University, 1091 Budapest, Hungary.
Zsuzsa
Z
Schaff
Gabor Lendvai, Zsuzsa Schaff, MTA-SE Tumor Progression Research Group, Semmelweis University, 1091 Budapest, Hungary.
András
A
Kiss
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001706:Biopsy; D016022:Case-Control Studies; D005260:Female; D005819:Genetic Markers; D019698:Hepatitis C, Chronic / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000821:virology; D006801:Humans; D008099:Liver / Q000737:chemistry* / Q000473:pathology / Q000821:virology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000821:virology; D012720:Severity of Illness Index; D015854:Up-Regulation; D005723:gamma-Glutamyltransferase / Q000097:blood
D005819:Genetic Markers; C546140:MIRN224 microRNA, human; C550416:MIRN33a microRNA, human; D035683:MicroRNAs; D005723:gamma-Glutamyltransferase; C554782:gamma-glutamyltransferase, human; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase
Chronic hepatitis C; Expression; MicroRNA; Steatosis; miR-224; miR-33a