A functional interaction between alpha-fetoprotein and miRNA-29 modulates the HCC epigenome

Thursday, October 11, 2012 — Poster Session III
10:00 a.m. – Noon	Natcher Conference Center, Building 45	NCI	GEN/GENOM-19

* FARE Award Winner

Authors

• S. Parpart
• S. Roessler
• F. Dong
• V. Rao
• C. Loffredo
• X.W. Wang

Abstract

Globally, hepatocellular carcinoma (HCC) accounts for 70-85% of primary liver cancers and ranks second in the leading cause of male cancer death. Serum alpha-fetoprotein (AFP) is a key HCC biomarker associated with poor patient outcome. We hypothesize that AFP+ and AFP- tumors may differ biologically and have a different prognosis in HCC patients. In this study, we performed microarray-based global microRNA (miRNA) and mRNA profiling analyses of 242 HCC cases that differ in AFP expression. We found that members of the miRNA-29 family are the most significantly (p<1E-5) down-regulated miRNAs in AFP+ tumors. In parallel, we found that a member of the DNA methyltransferase (DNMT) family, DNMT3A, is one of the most significantly (p=8E-6) up-regulated genes in AFP+ HCC. In addition, there is a significant inverse correlation (p<1E-4) between miR-29 and DNMT expression, suggesting that they may be functionally antagonistic, which is consistent with the recent finding showing that DNMT3A and DNMT3B are direct targets of miRNA-29. Moreover, HCC cases with elevated AFP and low miRNA-29 expression have an increased global DNA methylation. Identifying the molecular mechanisms linking AFP and miRNA-29 expression to epigenetic alterations in HCC may improve our understanding of HCC progression and reveal molecular targets for therapy.

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