Indeed, in addition to genetic and epigenetic abnormalities modifying oncogenes and tumor suppressor genes, deregulation of miRNAs has been shown to contribute to carcinogenesis of both solid and hematological

malignancy.4, 5 In recent years, significant efforts were taken to identify miRNAs that regulate hepatocarcinogenesis. Altered expression Ibrutinib in vivo patterns of miRNAs have been described in both rodent and human hepatocellular carcinoma (HCC) in studies using microarray technology or quantitative polymerase chain reaction (qPCR). In 2006, Murakami et al. reported on a panel of eight miRNAs that were significantly altered in HCC, comprising the miR-199 family, which was also down-regulated in their collective.6 In the following years, a whole kaleidoscope

of other deregulated miRNAs were reported by different groups in the context of HCC.7 Furthermore, specific targets were linked to miRNAs deregulated in HCC, including genes involved in tumor metastasis such as focal adhesion kinase (targeted by miR-151),8, 9 cell-cycle–modulating proteins such as cyclin G1 (targeted by miR-122),10 or the cyclin-dependent AZD8055 in vivo kinase inhibitors CDKN1B/p27 and CDKN1C/p57 (targeted by miR-221).11 However, as the authors of the present article point out, the results obtained from these previous microarray- or qPCR-based studies had certain limitations. They were at least partially controversial and demonstrated a large interstudy variance. In addition, they mainly focused on the alterations of individual miRNAs, but were unable to determine the abundance of each miRNA in the background of the entire miRNome. Based on the hypothesis that a minimum threshold amount must be reached for miRNAs to exert Protirelin their function,12 it seemed likely that the abundantly expressed miRNAs might be more important than those expressed at relatively low levels. In the present study by Hou and coworkers from the Second Military Medical University of Shanghai, China, the authors applied the innovative massively parallel signature sequencing

(MPSS) technology to carry out a comparative in-depth analysis of the miRNomes in normal liver tissues and HCC.13 This technique provides the unique possibility to identify the individual miRNome in-depth and thereby to reveal miRNA expression differences in relation to the individual miRNA abundances. Using this technique, the authors identified specific miRNAs that were most abundant in their collectives of normal liver, hepatitis-infected livers, and HCCs. Within this panel of miRNAs, miR-199a/b-3p was markedly decreased in HCC samples as compared with matched non-neoplastic liver tissues. The authors next validated these MPSS-based expression data in livers from different large and well-defined cohorts of patients with HCC by qPCR and correlated these data with clinical features.