Epigenetic silencing of microRNA genes has been shown to contribute substantially in carcinogenesis including heparocellular carcinoma (HCC), the fifth most common cancer and the third leading cause of cancer mortality worldwide.
Using DNMT knockdown and microRNA microarray profiling in HCC cell lines, we then perform DNA methylation and microRNA expression analysis in primary HCC tumor samples.
Using DNMT knockdown and microRNA profiling in HCC cell lines, we found that hsa-mir-183 is upregulated after the knockdown and confirmed this with qRT-PCR. Further analysis in primary HCC specimens showed that miR-183 is hypermethylated in 30% of HCC (n = 40). Expression of mature miR-183 showed an inverse correlation with the methylation levels. In HCC cells, DNMT knockdown and 5-aza-2'-deoxycytidine treatment reduced methylation and stimulated expression of miR-183. In HCC patients, hypermethylation at miR-183 promoter significantly correlates with poor survival (log rank test p = 0.03). DNA methylation analysis in healthy liver, benign liver tumors (HCA and FNH) showed absent of hypermethylation suggesting that aberrant miR-183 methylation is specific event in liver malignancy.
Our data indicate that hypermethylation in miR-183 is a frequent event in HCC and potentially useful as a new diagnostic and prognostic marker.
Clinical trial indentification
My study is not a clinical trial.
Legal entity responsible for the study
Department of Surgery Faculty of Medicine Universitas Gadjah Mada Hannover Medical School
DFG German Science Foundation
All authors have declared no conflicts of interest.