Abstract
The miRNAs play important regulating roles in the pathogenesis of hepatocellular carcinoma (HCC). To uncover key regulating miRNAs in HCC that were neglected by traditional analyzing methods of transcriptomics data, we proposed a novel molecular-network-based omics’ (MNBO) method. With this method, we predicted HCC-regulating miRNAs, and confirmed the role of a novel miR-590-3P/EED axis by a clinical study and in vitro, in vivo wet-experiments. The miR-590-3P is significantly down-regulated in HCC patients. And low level of miR-590-3P in HCC is associated with poor prognosis of patients. In HCC cell lines, the miR-590-3P suppressed cell proliferation by inhibiting the transformation G1 phase to S phases of the cell cycle. Moreover, the miR-590-3P inhibited migration and invasion of HCC cells. Further investigations indicated that miR-590-3P play its roles by inhibiting polycomb protein EED. The experiments in animal model implied miR-590-3P could be a potential therapeutic agent for HCC in the future. In conclusion, the discovery of miR-590-3P revealed the MNBO would be a useful strategy to uncover key regulating miRNAs in HCC.
Highlights
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death of human [1, 2]
To score the importance of selected miRNAs to the pathogenesis of HCC, we proposed a novel molecularnetwork-based omics’ method (MNBO)
Positive MNBO score indicates the miRNA is up-regulated in HCC, while a negative one reveals the miRNA is down-regulated
Summary
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death of human [1, 2]. Various high-throughput transcriptomics studies were performed to investigate potential key regulating miRNAs in the pathogenesis of HCC [5, 6]. Fold change and T-test were most common used methods to select candidate miRNAs in these studies. These methods would select tens to hundreds of miRNAs that may be involved in HCC. They couldn’t indicate the importance of selected miRNAs to the pathogenesis of HCC. It’s quite difficult to select miRNA for wet-experiments from the candidate miRNAs, and many key regulating miRNAs in HCC might be neglected in this process
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