CircCUL2 induces an inflammatory CAF phenotype in pancreatic ductal adenocarcinoma via the activation of the MyD88-dependent NF-κB signaling pathway.

ABSTRACT:

Background

Pancreatic ductal adenocarcinoma (PDAC) is characterized by clusters of cancer cells surrounded by a dense desmoplastic stroma. However, little is known about stromal cell heterogeneity in the pancreatic tumor microenvironment.

Methods

We conducted circRNA profiling in primary fibroblasts by high-throughput sequencing and detected circCUL2 levels in PDAC tissues by qRT-PCR. We subsequently investigated the effect of circCUL2 on inflammatory cancer-associated fibroblast (iCAF) activation, heterogeneity and protumor activity by ELISA, flow cytometry, colony formation and transwell assays in vitro and by xenograft models in vivo. The regulatory effect of circCUL2 on miR-203a-3p/MyD88/IL6 was examined by RNA pulldown, FISH, and luciferase reporter assays.

Results</

SUBMITTER: Zheng S 

PROVIDER: S-EPMC8862589 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature