Cancers, Vol. 14, Pages 1848: HuR Plays a Role in Double-Strand Break Repair in Pancreatic Cancer Cells and Regulates Functional BRCA1-Associated-Ring-Domain-1(BARD1) Isoforms
Cancers, Vol. 14, Pages 1848: HuR Plays a Role in Double-Strand Break Repair in Pancreatic Cancer Cells and Regulates Functional BRCA1-Associated-Ring-Domain-1(BARD1) Isoforms
Cancers doi: 10.3390/cancers14071848
Authors:
Aditi Jain
Matthew McCoy
Carolyn Coats
Samantha Z. Brown
Sankar Addya
Carl Pelz
Rosalie C. Sears
Charles J. Yeo
Jonathan R. Brody
Human Antigen R (HuR/ELAVL1) is known to regulate stability of mRNAs involved in pancreatic ductal adenocarcinoma (PDAC) cell survival. Although several HuR targets are established, it is likely that many remain currently unknown. Here, we identified BARD1 mRNA as a novel target of HuR. Silencing HuR caused a >70% decrease in homologous recombination repair (HRR) efficiency as measured by the double-strand break repair (pDR-GFP reporter) assay. HuR-bound mRNAs extracted from RNP-immunoprecipitation and probed on a microarray, revealed a subset of HRR genes as putative HuR targets, including the BRCA1-Associated-Ring-Domain-1 (BARD1) (p < 0.005). BARD1 genetic alterations are infrequent in PDAC, and its context-dependent upregulation is poorly understood. Genetic silencing (siRNA and CRISPR knock-out) and pharmacological targeting of HuR inhibited both full length (FL) BARD1 and its functional isoforms (α, δ, Φ). Silencing BARD1 sensitized cells to olaparib and oxaliplatin; caused G2-M cell cycle arrest; and increased DNA-damage while decreasing H...
Source: Cancers - Category: Cancer & Oncology Authors: Aditi Jain Matthew McCoy Carolyn Coats Samantha Z. Brown Sankar Addya Carl Pelz Rosalie C. Sears Charles J. Yeo Jonathan R. Brody Tags: Article Source Type: research
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