Cancer-associated fibroblast-induced lncRNA UPK1A-AS1 confers platinum resistance in pancreatic cancer via efficient double-strand break repair.

ABSTRACT: The tumor stroma of pancreatic ductal adenocarcinoma (PDAC) is characterized by an abundant and heterogeneous population of cancer-associated fibroblasts (CAFs), which are critically involved in chemoresistance. However, the underlying mechanism of CAFs in chemoresistance is unclear. Here, we show that CAF^R, a CAF subset derived from platinum-resistant PDAC patients, assumes an iCAF phenotype and produces more IL8 than CAF^S isolated from platinum-sensitive PDAC patients. CAF^R-derived IL8 promotes oxaliplatin chemoresistance in PDAC. Based on long noncoding RNA (lncRNA) profiling in tumor cells incubated with CAF-CM, we found that UPK1A-AS1, whose expression is directly induced by IL8/NF-kappa B signaling, functions as a chemoresistance-promoting lncRNA and

SUBMITTER: Zhang X 

PROVIDER: S-EPMC9010302 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature