Circ_0018909 knockdown inhibits the development of pancreatic cancer via the miR-545-3p/FASN axis and reduces macrophage polarization to M2.

ABSTRACT

Multiple circular RNAs (circRNAs) were proven to regulate the development of pancreatic cancer. However, the action of circ_0018909 in pancreatic cancer was still unclear. The expression of circ_0018909, microRNA-545-3p (miR-545-3p), and fatty acid synthase (FASN) was measured using quantitative reverse-transcriptase PCR (qRT-PCR). Cell growth, cell cycle arrest, apoptotic cells, metastasis, and epithelial to mesenchymal transition (EMT) were determined using EdU assay, flow cytometry, wound-healing assay, transwell invasion, and western blotting, respectively. The expression of the macrophage markers, including CD80, MCP-1, iNOS, and IL-6 (M1 markers), as well as CD206 and CD163 (M2 markers), was analyzed using qRT-PCR. Circ_0018909 knockdown dramatically depressed cell growth, migration, invasion, EMT, and elevated the number of apoptotic cells in pancreatic cancer cells, and repressed tumor growth in mice. Moreover, we proved that the absence of miR-545-3p rescued the action of circ_0018909 downregulation on cell growth, metastasis, apoptosis, and EMT in pancreatic cancer cells. MiR-545-3p bound to FASN and FASN overexpression hindered the impacts of miR-545-3p on the progression of pancreatic cancer. Besides this, our data demonstrated that circ_0018909 induced polarization from M0 macrophages to M2 macrophages. Circ_0018909 knockdown retarded the development of pancreatic cancer by modulating miR-545-3p to regulate FASN expression.