Transcriptomics

Dataset Information

0

Whole-gene transcriptome profiling of Panc-1 which were treated with conditinal meida (CM) from CAFS or CAFR


ABSTRACT: Tumor stroma of pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant and heterogeneous cancer-associated fibroblasts (CAFs) that are critically involved in chemoresistance. However, the underlying mechanism of CAFs in chemoresistance is unclear. Here, we show that CAFR, a CAFs subset derived from oxaliplatin-resistant PDAC patients, produces more IL8 than CAFS isolated form oxaliplatin-sensitive PDAC patients. CAFR derived IL8 promotes PDAC oxaliplatin chemoresistance. Base on long non-coding RNA (lncRNA) profiling in tumor cells incubated with CAF, we identify that UPK1A-AS, which is directly induced by IL8/NF-kappa B signaling, functions as a pro-chemoresistant lncRNA and is critical for active IL8-induced oxaliplatin resistance. Impressively, blocking UPK1A-AS1 activation increases sensitivity of tumor cell response to oxaliplatin chemotherapy in vivo. Mechanically, UPK1A-AS1 strengths the interaction of Ku70 and Ku80 to enhance double-strand DNA break (DSB) repair, thereby coordinating the NHEJ pathway. Clinically, UPK1A-AS1 expression is positively correlated with IL8 expression, poor chemotherapeutic response and shorter PFS of PDAC patients. Collectively, our study discovers a lncRNA-mediated mechanism for CAF derived IL8 paracrine-dependent oxaliplatin resistance and highlights UPK1A-AS1 as potential therapeutic targets.

ORGANISM(S): Homo sapiens

PROVIDER: GSE183779 | GEO | 2021/09/16

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2024-10-06 | E-MTAB-14494 | biostudies-arrayexpress
2016-11-01 | GSE85048 | GEO
2018-10-27 | GSE121848 | GEO
| EGAS00001006661 | EGA
| phs001840 | dbGaP
2022-08-23 | GSE197908 | GEO
2024-04-29 | GSE265764 | GEO
2024-10-30 | GSE280564 | GEO
2024-06-21 | GSE255978 | GEO
2024-03-15 | GSE254384 | GEO