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Cited by 80MicroRNA in disease regulationCancer-related molecular mechanisms researchRNA Research and Splicing

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

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Luna, Joseph M., Barajas, Juan M., Teng, Kun-yu, Sun, Hui-Lung, Moore, Michael J., Rice, Charles M., Darnell, Robert B., Ghoshal, Kalpana·2017·Molecular Cell
DOI 10.1016/j.molcel.2017.06.025PMC PMC5603316
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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.

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  • miR-122 antagonizes the expression of a large proportion of hepatic mRNAs that encode for a variety of developmental, metabolic, and homeostatic functions.

    “miR-122 antagonizes the expression of a large proportion of hepatic mRNAs that encode for a variety of developmental, metabolic, and homeostatic functions (Luna et al. 2017).”

    From ESRP2–microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation (2025) · cites this paper as Luna et al. 2017

    The Introduction (page not available) says miR-122 represses hundreds of target mRNAs and regulates transcripts involved in diverse hepatic processes, including metabolism and polyploidy; it also describes a role in hepatic homeostasis. It does not establish that those targets constitute a large proportion of all hepatic mRNAs. The Results further distinguish miR-122 binding from measurable repression of target expression. (LLM, conf=0.82)

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Cited by

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Authors
Luna, J. M., Barajas, J. M., Teng, K.-Y., Sun, H.-L., Moore, M. J., Rice, C. M., Darnell, R. B., & Ghoshal, K.
Affiliations
  • Howard Hughes Medical Institute (US)
  • The Ohio State University (US)
  • Rockefeller University (US)
  • The Ohio State University Wexner Medical Center (US)
Corresponding author
  • Darnell, Robert B.
  • Ghoshal, Kalpana
ORCID
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2017-08
Volume
67
Issue
3
Pages
400-410.e7
ISSN
1097-2765 (ISSN-L)
DOI
10.1016/j.molcel.2017.06.025
PMC
PMC5603316
OpenAlex
W2738618087
Cited by
80
References
7
Citations by year
2026: 2 · 2025: 8 · 2024: 9 · 2023: 5 · 2022: 7 · 2021: 9 · 2020: 17 · 2019: 11 · 2018: 10 · 2017: 2
FWCI
3.67
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • NIH (R01CA193244, R01CA086978, R01NS034389, R01NS081706, R35NS097404)
  • Pelotonia Idea
  • Pelotonia
  • NIAID (R01AI116943)
  • Howard Hughes Medical Institute
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords
miR-122, miRNA targetome, hepatocellular carcinoma, liver cancer, 3' UTR binding, BCL9, patient survival, microRNA binding sites, tumor suppressor microRNA
MeSH terms
Animals, Binding Sites, Exons, Genotype, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Neoplasm Proteins, Phenotype, Species Specificity, Time Factors, Transcription Factors, Transcription, Genetic, Transfection, Down-Regulation, Gene Expression Regulation, Neoplastic, Case-Control Studies, Mice, Knockout, Computational Biology, 3' Untranslated Regions, Databases, Genetic, RNA Interference, MicroRNAs, Cell Line, Tumor, Immunoprecipitation, Intracellular Signaling Peptides and Proteins, Cell Proliferation, Mice, Genome-Wide Association Study, Transcriptome, Wnt Signaling Pathway, Argonaute Proteins

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