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Argonaute CLIP defines a deregulated miR-122 bound transcriptome that correlates with patient survival in human liver cancer

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE97061 | GEO | 2017/03/28

SECONDARY ACCESSION(S): PRJNA380605

REPOSITORIES: GEO

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Argonaute CLIP Defines a Deregulated miR-122-Bound Transcriptome that Correlates with Patient Survival in Human Liver Cancer.

Project description: Not available

| S-EPMC5603316 | biostudies-literature

Argonaute CLIP defines a deregulated miR-122 bound transcriptome that correlates with patient survival in human liver cancer (Human CLIP-Seq)

Project description:MicroRNA-122, an abundant and conserved liver-specific miRNA, regulates hepatic metabolism and functions as a tumor suppressor, yet systematic and direct biochemical elucidation of the miR-122 target network remains incomplete. To this end, we performed Argonaute crosslinking immunoprecipitation (Ago-CLIP) sequencing in miR-122 knockout and control mouse livers, as well as in matched human hepatocellular carcinoma (HCC) and benign liver tissue to identify miRNA target sites transcriptome-wide in two species. We observed a majority of miR-122 binding on 3’-UTRs and coding exons followed by extensive binding to other genic and non-genic sites. Motif analysis of miR-122 dependent binding revealed a novel G-bulged motif in addition to canonical motifs. A large number of miR-122 targets were found to be species-specific. Upregulation of several common mouse and human targets, most notably BCL9, predicted survival in HCC patients. These results broadly define the molecular consequences of miR-122 downregulation in hepatocellular carcinoma.

2017-03-28 | GSE97056 | GEO

Argonaute CLIP defines a deregulated miR-122 bound transcriptome that correlates with patient survival in human liver cancer (Mouse CLIP-Seq)

2017-03-28 | GSE97058 | GEO

Argonaute CLIP defines a deregulated miR-122 bound transcriptome that correlates with patient survival in human liver cancer (Mouse RNA-Seq)

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Argonaute CLIP defines a deregulated miR-122 bound transcriptome that correlates with patient survival in human liver cancer

Project description:Argonaute CLIP defines a deregulated miR-122 bound transcriptome that correlates with patient survival in human liver cancer

| PRJNA380605 | ENA

Hepatitis C virus functionally sequesters miR-122 [miR-122 KO vs Control CLIP]

Project description:Hepatitis C virus uniquely requires the liver specific microRNA-122 for replication, yet global effects on endogenous miRNA targets during infection are unexplored. Here, high-throughput sequencing and crosslinking immunoprecipitation (HITS-CLIP) experiments of human Argonaute (Ago) during HCV infection showed robust Ago binding on the HCV 5’UTR, at known and predicted miR-122 sites. On the human transcriptome, we observed reduced Ago binding and functional mRNA de-repression of miR-122 targets during virus infection. This miR-122 “sponge” effect could be relieved and redirected to miR-15 targets by swapping the miRNA tropism of the virus. Single-cell expression data from reporters containing miR-122 sites showed significant de-repression during HCV infection depending on expression level and number of sites. We describe a quantitative mathematical model of HCV induced miR-122 sequestration and propose that such miR-122 inhibition by HCV RNA may result in global de-repression of host miR-122 targets, providing an environment fertile for the long-term oncogenic potential of HCV.

2015-01-06 | GSE64679 | GEO