Long non-coding RNA in liver of HCC mouse model
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE78911 | GEO | 2017/08/31
SECONDARY ACCESSION(S): PRJNA314342
REPOSITORIES: GEO
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Project description:Although many protein-coding genes have been identified to be aberrantly expressed in hepatocellular carcinoma (HCC), the mechanisms that account for development and progression of HCC remain unclear. In recent years, long noncoding RNAs (lncRNAs) have been shown to have critical regulatory roles in mammalian cell biology. Many lncRNAs can result in aberrant expression of gene products that may contribute to cancer biology. In this study, we first identified non-overlapping signatures of a small number of lncRNAs that are aberrantly expressed in human HCC compared with paired peritumoral tissues. Then we used real-time PCR to validate five lncRNAs whose expression was altered in HCC compared with paired peritumoral tissues. Using loss-of-function and gain-of-function approaches, we found that an lncRNA (termed lncRNA-HEIH) plays a key role in cell cycle regulation. We further demonstrated that lncRNA-HEIH bound to enhancer of zeste homolog 2 (EZH2) and that this interaction was required for the repression of EZH2 target genes. Together, these results reveal insights into the molecular regulation mechanisms of HCC cell cycle regulation and lead us to propose that lncRNAs may serve as key regulatory hubs in cancer biology. A ten chip study using total RNA recovered from five separate HCC tissues and five corresponding paired non-tumor samples.
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Project description:Although many protein-coding genes have been identified to be aberrantly expressed in hepatocellular carcinoma (HCC), the mechanisms that account for development and progression of HCC remain unclear. In recent years, long noncoding RNAs (lncRNAs) have been shown to have critical regulatory roles in mammalian cell biology. Many lncRNAs can result in aberrant expression of gene products that may contribute to cancer biology. In this study, we first identified non-overlapping signatures of a small number of lncRNAs that are aberrantly expressed in human HCC compared with paired peritumoral tissues. Then we used real-time PCR to validate five lncRNAs whose expression was altered in HCC compared with paired peritumoral tissues. Using loss-of-function and gain-of-function approaches, we found that an lncRNA (termed lncRNA-HEIH) plays a key role in cell cycle regulation. We further demonstrated that lncRNA-HEIH bound to enhancer of zeste homolog 2 (EZH2) and that this interaction was required for the repression of EZH2 target genes. Together, these results reveal insights into the molecular regulation mechanisms of HCC cell cycle regulation and lead us to propose that lncRNAs may serve as key regulatory hubs in cancer biology.
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