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Cell Rep. 2016 May 31;15(9):1876-83. doi: 10.1016/j.celrep.2016.04.083. Epub 2016 May 19.

IGF2BP3 Modulates the Interaction of Invasion-Associated Transcripts with RISC.

Author information

1
Department of Molecular, Cellular and Developmental Biology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA; The Donnelly Centre, University of Toronto, Toronto, ON M5S 1A1, Canada.
2
Department of Molecular, Cellular and Developmental Biology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA.
3
Department of Molecular, Cellular and Developmental Biology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA; Department of Genetics, Stanford University, 3165 Porter Drive, Palo Alto, CA 94304, USA.
4
Molecular and Computational Biology Section, Division of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
5
Center for Biomolecular Science and Engineering, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA.
6
Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
7
Bioo Scientific Corporation, 7500 Burleston Road, Austin, TX 78744, USA.
8
The Donnelly Centre, University of Toronto, Toronto, ON M5S 1A1, Canada.
9
Department of Molecular, Cellular and Developmental Biology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060, USA. Electronic address: jsanfor2@ucsc.edu.

Abstract

Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) expression correlates with malignancy, but its role(s) in pathogenesis remains enigmatic. We interrogated the IGF2BP3-RNA interaction network in pancreatic ductal adenocarcinoma (PDAC) cells. Using a combination of genome-wide approaches, we have identified 164 direct mRNA targets of IGF2BP3. These transcripts encode proteins enriched for functions such as cell migration, proliferation, and adhesion. Loss of IGF2BP3 reduced PDAC cell invasiveness and remodeled focal adhesion junctions. Individual nucleotide resolution crosslinking immunoprecipitation (iCLIP) revealed significant overlap of IGF2BP3 and microRNA (miRNA) binding sites. IGF2BP3 promotes association of the RNA-induced silencing complex (RISC) with specific transcripts. Our results show that IGF2BP3 influences a malignancy-associated RNA regulon by modulating miRNA-mRNA interactions.

PMID:
27210763
PMCID:
PMC4889463
DOI:
10.1016/j.celrep.2016.04.083
[Indexed for MEDLINE]
Free PMC Article

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