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

Molecular cell | Aug 3, 2017

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 (Argonaute [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 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.

Pubmed ID: 28735896 RIS Download

Mesh terms: 3' Untranslated Regions | Animals | Argonaute Proteins | Binding Sites | Carcinoma, Hepatocellular | Case-Control Studies | Cell Line, Tumor | Cell Proliferation | Computational Biology | Databases, Genetic | Down-Regulation | Exons | Gene Expression Regulation, Neoplastic | Genome-Wide Association Study | Genotype | Humans | Immunoprecipitation | Intracellular Signaling Peptides and Proteins | Liver Neoplasms | Mice | Mice, Knockout | MicroRNAs | Neoplasm Proteins | Phenotype | RNA Interference | Species Specificity | Time Factors | Transcription, Genetic | Transcriptome | Transfection | Wnt Signaling Pathway

Data used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, Id: R01 CA086978
  • Agency: NINDS NIH HHS, Id: R01 NS081706
  • Agency: NIAID NIH HHS, Id: R01 AI116943
  • Agency: NINDS NIH HHS, Id: R01 NS034389
  • Agency: NINDS NIH HHS, Id: R35 NS097404
  • Agency: NCI NIH HHS, Id: R01 CA193244

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