Abstract:
:Human antigen R (ELAVL1; HuR) is perhaps the best-characterized RNA-binding protein. Through its overexpression in various tumor types, HuR promotes posttranscriptional regulation of target genes in multiple core signaling pathways associated with tumor progression. The role of HuR overexpression in pancreatic tumorigenesis is unknown and led us to explore the consequences of HuR overexpression using a novel transgenic mouse model that has a >2-fold elevation of pancreatic HuR expression. Histologically, HuR-overexpressing pancreas displays a fibroinflammatory response and other pathological features characteristic of chronic pancreatitis. This pathology is reflected in changes in the pancreatic gene expression profile due, in part, to genes whose expression changes as a consequence of direct binding of their respective mRNAs to HuR. Older mice develop pancreatic steatosis and severe glucose intolerance. Elevated HuR cooperated with mutant K-rasG12D to result in a 3.4-fold increase in pancreatic ductal adenocarcinoma (PDAC) incidence compared to PDAC presence in K-rasG12D alone. These findings implicate HuR as a facilitator of pancreatic tumorigenesis, especially in the setting of inflammation, and a novel therapeutic target for pancreatitis treatment.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Peng W,Furuuchi N,Aslanukova L,Huang YH,Brown SZ,Jiang W,Addya S,Vishwakarma V,Peters E,Brody JR,Dixon DA,Sawicki JAdoi
10.1128/MCB.00427-17subject
Has Abstractpub_date
2018-01-16 00:00:00issue
3eissn
0270-7306issn
1098-5549pii
MCB.00427-17journal_volume
38pub_type
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