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

Overview

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.

publication date

  • July 20, 2017

Research

keywords

  • Argonaute Proteins
  • Carcinoma, Hepatocellular
  • Immunoprecipitation
  • Liver Neoplasms
  • MicroRNAs
  • Transcriptome

Identity

PubMed Central ID

  • PMC5603316

Scopus Document Identifier

  • 85025426270

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2017.06.025

PubMed ID

  • 28735896

Additional Document Info

volume

  • 67

issue

  • 3