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

Joseph M. Luna, Juan M. Barajas, Kun yu Teng, Hui Lung Sun, Michael J. Moore, Charles M. Rice, Robert B. Darnell, Kalpana Ghoshal

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23 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)400-410.e7
JournalMolecular Cell
Volume67
Issue number3
DOIs
Publication statusPublished - 3 Aug 2017

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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