Identifying key regulating miRNAs in hepatocellular carcinomas by an omics’ method
نویسندگان
چکیده
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.
منابع مشابه
The Role of miRNA Dysregulation in Thyroid Cancer Development by Targeting the Main Signaling Pathways
Thyroid cancer is one of the most common malignancies of endocrine glands, causing carcinomas, such as papillary, follicular, medullary, and anaplastic thyroid carcinomas. Due to the significance of thyroid carcinomas, identification of the main signaling pathways and the affecting mutations has been considered by researchers. Further studies on the dysregulation of oncogenes in signaling path...
متن کاملSubpathway-GMir: identifying miRNA-mediated metabolic subpathways by integrating condition-specific genes, microRNAs, and pathway topologies.
MicroRNAs (miRNAs) regulate disease-relevant metabolic pathways. However, most current pathway identification methods fail to consider miRNAs in addition to genes when analyzing pathways. We developed a powerful method called Subpathway-GMir to construct miRNA-regulated metabolic pathways and to identify miRNA-mediated subpathways by considering condition-specific genes, miRNAs, and pathway top...
متن کاملGlobal regulation on microRNA in hepatitis B virus-associated hepatocellular carcinoma.
Recent work has revealed the causative links between deregulation of microRNAs (miRNAs) and cancer development. In hepatocellular carcinoma (HCC), aberrant expression of miRNAs has been observed, but the molecular mechanisms that contribute to such changes remains to be elucidated. Here, we reported the analysis of miRNA expression in 94 pairs of tumor and adjacent nontumor tissues from HBV-ass...
متن کاملiSubgraph: Integrative Genomics for Subgroup Discovery in Hepatocellular Carcinoma Using Graph Mining and Mixture Models
The high tumor heterogeneity makes it very challenging to identify key tumorigenic pathways as therapeutic targets. The integration of multiple omics data is a promising approach to identify driving regulatory networks in patient subgroups. Here, we propose a novel conceptual framework to discover patterns of miRNA-gene networks, observed frequently up- or down-regulated in a group of patients ...
متن کاملmiR-92a promotes hepatocellular carcinoma cells proliferation and invasion by FOXA2 targeting
Objective(s): MicroRNAs (miRNAs) are considered as powerful, post-transcriptional regulators of gene expression in hepatocellular carcinoma cells (HCC). However, the function of miR-92a is still unclear in HCC. Materials and Methods: Expression of miR-92a in human HCC cell lines was evaluated using qRT-PCR. MTT assay and transwell assay were used to examine the function of miR-92a in HepG2 and ...
متن کامل