CircSFMBT1 promotes pancreatic cancer growth and metastasis via targeting miR-330-5p/PAK1 axis.

Abstract

Pancreatic cancer (PC) is one of the most common and lethal cancers that affects millions of people around the world. The prognosis of PC is poor with very limited effective treatments. Here, we fully investigated the function and underlying mechanism of circSFMBT1 (hsa_circ_0066147) in PC. Real-time quantitative PCR, Western blotting, and immunohistochemistry were used to examine levels of circSFMBT1, miR-330-5p, PAK1 (p21-activated kinase 1), or proliferation/metastasis-related proteins. Colony formation assay, flow cytometry, and transwell assay detected the roles of circSFMBT1 and miR-330-5p in cell apoptosis, proliferation, migration, and invasion of PC cells, respectively. Dual luciferase assay and RNA immunoprecipitation were used to validate the interactions of circSFMBT1/miR-330-5p and miR-330-5p/PAK1. Fluorescence in situ hybridization was performed to examine the subcellular localization of circSFMBT1 and miR-330-5p. Subcutaneous tumor growth was monitored in nude mice and in vivo metastasis was examined as well following injection of PC cells into the tail vein. This study demonstrated that circSFMBT1 and PAK1 were up-regulated in PC tissues and cells, while miR-330-5p was down-regulated. circSFMBT1 directly bound miR-330-5p and inhibited its expression. In addition, circSFMBT1 promoted proliferation, migration, and invasion of PC cells through up-regulating proliferation-related proteins and down-regulating apoptosis-related proteins via miR-330-5p. miR-330-5p directly bound PAK1 mRNA and suppressed proliferation, migration, invasion, and epithelial-mesenchymal transition process via targeting PAK1 in PC cells. Further, knockdown circSFMBT1 increased miR-330-5p level, but decreased PAK1 expression and repressed tumor growth and metastasis in vivo. Taken together, circSFMBT1 promotes proliferation and metastasis of PC via regulating miR-330-5p/PAK1 pathway as a miR-330-5p sponge.