Conclusion
This study highlights that down-regulated miR-223 or elevated ZIC1 inhibits the development of PC via restricting activation of the PI3K/Akt/mTOR pathway, which has important meanings for exploring the mechanism of PC.
Methods
MiR-223 and ZIC1 expression in PC tissue and cell lines was detected. PANC-1 cells and SW1990 cells were screened for subsequent experiments. Screened cells were transfected with miR-223- or ZIC1-related oligonucleotides or plasmids, or AZD8055, the dual inhibitor of the PI3K/Akt/mTOR signaling pathway to test the functions of miR-223, ZIC1 or PI3K/Akt/mTOR signaling pathway in the biological functions of PC cells. The expression of miR-223, ZIC1, or PI3K/Akt/mTOR signaling pathway-related proteins was examined. Tumor xenograft in nude mice was conducted for the detection of tumor growth of PC.
Objective
MicroRNAs (miRNAs) are known to participate in the progression of human cancers, such as pancreatic cancer (PC), while the mechanisms of miR-223 in PC remain largely unknown. This study was for the investigation of the status of microRNA (miR)-223 in the growth of PC with the involvement of ZIC1 and the PI3K/Akt/mTOR pathway.
Results
Up-regulated miR-223 and declined ZIC1 existed in PC tissues of patients and cell lines. ZIC1 was determined to be a target gene of miR-223. Down-regulated miR-223 or up-regulated ZIC1 led to suppressed proliferation, migration, invasion, and cell cycle entry, volume and weight of tumors, while elevated apoptosis in PC cells through declining phosphorylation levels of PI3K, Akt and mTOR. MiR-223 up-regulation or ZIC1 down-regulation induced opposite results on PC cells.