Case Control Study
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World J Gastroenterol. Nov 7, 2014; 20(41): 15343-15350
Published online Nov 7, 2014. doi: 10.3748/wjg.v20.i41.15343
Elevated miR-33a and miR-224 in steatotic chronic hepatitis C liver biopsies
Gabor Lendvai, Katalin Jármay, Gizella Karácsony, Tünde Halász, Ilona Kovalszky, Kornélia Baghy, Tibor Wittmann, Zsuzsa Schaff, András Kiss
Gabor Lendvai, Zsuzsa Schaff, MTA-SE Tumor Progression Research Group, Semmelweis University, 1091 Budapest, Hungary
Katalin Jármay, Gizella Karácsony, Tibor Wittmann, 1st Department of Medicine, University of Szeged, 6720 Szeged, Hungary
Tünde Halász, Zsuzsa Schaff, András Kiss, 2nd Department of Pathology, Semmelweis University, 1091 Budapest, Hungary
Ilona Kovalszky, Kornélia Baghy, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, Hungary
Author contributions: Jármay K, Schaff Z and Kiss A designed the study; Jármay K, Karácsony G, Kovalszky I, Wittmann T, Schaff Z and Kiss A chose and diagnosed the patient samples; Lendvai G, Karácsony G and Halász T performed the research; Lendvai G, Jármay K, Karácsony G, Kovalszky I, Baghy K, Schaff Z and Kiss A analyzed and interpreted the data; Lendvai G, Schaff Z and Kiss A wrote the paper; all authors critically reviewed and approved the manuscript.
Supported by Grants from the National Scientific Research Fund, No. OTKA K101435, No. K108548 and No. 105763
Correspondence to: Zsuzsa Schaff, MD, PhD, DSc, Professor of Pathology, 2nd Department of Pathology, Semmelweis University, Ulloi 93, 1091 Budapest, Hungary.
Telephone: +36-1-215-6921 Fax: +36-1-215-6921
Received: February 11, 2014
Revised: May 7, 2014
Accepted: June 13, 2014
Published online: November 7, 2014

AIM: 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.

CONCLUSION: 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.

Keywords: Chronic hepatitis C, Steatosis, MicroRNA, Expression, miR-33a, miR-224

Core tip: Chronic hepatitis C (CHC) and steatosis are liver diseases that can progress into hepatocellular carcinoma. In the current study, differences were found in expression of selected microRNAs in biopsy samples of steatotic liver, CHC-infected, and steatotic CHC-infected liver, compared to control samples. Interestingly, levels of miR-224, which are increased in hepatocellular carcinoma, were elevated in both types of steatotic liver when compared with normal or CHC-infected only liver tissues, and may be an indicator of a precancerous state.