Targeting the mRNA-binding protein HuR impairs malignant characteristics of pancreatic ductal adenocarcinoma cells

Oncotarget
Masaya JimboJonathan R Brody

Abstract

Post-transcriptional regulation is a powerful mediator of gene expression, and can rapidly alter the expression of numerous transcripts involved in tumorigenesis. We have previously shown that the mRNA-binding protein HuR (ELAVL1) is elevated in human pancreatic ductal adenocarcinoma (PDA) specimens compared to normal pancreatic tissues, and its cytoplasmic localization is associated with increased tumor stage. To gain a better insight into HuR's role in PDA biology and to assess it as a candidate therapeutic target, we altered HuR expression in PDA cell lines and characterized the resulting phenotype in preclinical models. HuR silencing by short hairpin and small interfering RNAs significantly decreased cell proliferation and anchorage-independent growth, as well as impaired migration and invasion. In comparison, HuR overexpression increased migration and invasion, but had no significant effects on cell proliferation and anchorage-independent growth. Importantly, two distinct targeted approaches to HuR silencing showed marked impairment in tumor growth in mouse xenografts. NanoString nCounter® analyses demonstrated that HuR regulates core biological processes, highlighting that HuR inhibition likely thwarts PDA viability throu...Continue Reading

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Citations

Jun 3, 2016·Wiley Interdisciplinary Reviews. RNA·Khalid S A Khabar
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Jul 6, 2019·Cancer Research·Aditi JainJonathan R Brody
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Methods Mentioned

BETA
transfection
transfections
xenograft
xenografts
PCR
PCA
immunoprecipitation
PAR-CLIP
Protein Assay
Infrared Imaging

Software Mentioned

Odyssey Infrared Imaging System
ImageJ
MeV
Database for Annotation , Visualization , and Integrated Disco...
TM4

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