Circ_0006790 carried by bone marrow mesenchymal stem cell-derived exosomes regulates S100A11 DNA methylation through binding to CBX7 in pancreatic ductal adenocarcinoma.

Extracellular vesicles, particularly exosomes, play a vital role via their cargoes. Their potential in pancreatic ductal adenocarcinoma (PDAC), one of the leading causes of cancer-related mortality worldwide is attracting interests. However, the roles and underlying mechanisms of exosomal circular RNAs (circRNAs) in the development of PDAC remain unclear yet. We aimed to illuminate the mechanisms of exosomal hsa_circ_0006790 (thereafter termed circ_6790) released by exosomes (Exo) derived from bone marrow mesenchymal stem cell (BM-MSC) during immune escape in PDAC in this study. BM-MSC-derived Exo inhibited growth, metastasis, and immune escape in PDAC. Exo enhanced circ_6790 expression in PDAC cells. Knockdown of circ_6790 in Exo significantly attenuated the anti-tumor effect of Exo. Circ_6790 facilitated the nuclear translocation of chromobox 7 (CBX7). CBX7 increased the DNA methylation of S100A11 by recruiting DNA methyltransferases to its promoter region, thereby inhibiting the transcription of S100A11. Inhibition of CBX7 or overexpression of S100A11 annulled the inhibitory effects of Exo on PDAC growth, metastasis, and immune escape. In conclusion, our results suggest that MSC-derived exosomal circ_6790 could downregulate S100A11 in PDAC cells and hamper immune escape via CBX7-catalyzed DNA hypermethylation. AJCR