MiR-573 suppresses cell proliferation, migration and invasion via regulation of E2F3 in pancreatic cancer.

ABSTRACT

Background: Pancreatic cancer is among the most lethal malignancies worldwide. In this study, we aimed to determine whether miR-573 could suppress pancreatic cancer cell proliferation, migration, and invasion by targeting E2F3. Materials and Methods: MiR-573 expression in pancreatic cancer tissues and cell lines was measured using real-time PCR. Target genes of miR-573 were screened using bioinformatics tools and confirmed using dual-luciferase reporter assay and real-time PCR. Pancreatic cancer cells were transfected using an miR-573 mimic or siRNA E2F3. Furthermore, cell proliferation, migration, and invasion were assessed using CCK-8, Edu staining, colony-forming assay, wound healing assay, and transwell assay in vitro. The in vivo effects of miR-573 were verified using tumor xenografts. Differential expression and prognostic analyses of miR-573 and E2F3 were visualized using the Kaplan­Meier plotter and GEPIA. Results: We found that the expression of miR-573 was significantly reduced in pancreatic cancer tissues and cell lines. Overexpression of miR-573 obviously suppressed the proliferation, migration, and invasion of pancreatic cancer cells. The Dual-luciferase assay showed that miR-573 could specifically target E2F3. Furthermore, E2F3 was up-regulated in pancreatic cancer tissues and cell lines and E2F3 down-regulation inhibited the proliferation, migration, and invasion of pancreatic cancer cells. The ectopic expression of miR-573 inhibited xenograft tumor growth in vivo. Results from the Kaplan-Meier analysis and GEPIA showed that patients with a high level of miR-573 had a significantly reduced risk of death while those with a high level of E2F3 displayed significant correlation with the tumor stage and suffered worse prognosis. Conclusions: MiR-573 could suppress the proliferation, migration, and invasion of pancreatic cancer cells by targeting E2F3, thereby establishing miR-573 as a novel regulator of E2F3 and indicating its critical role in tumorigenesis, especially in pancreatic cancer.