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

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. 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 . The effects of miR-573 were verified using tumor xenografts. Differential expression and prognostic analyses of miR-573 and E2F3 were visualized using the Kaplan‑Meier plotter and GEPIA. 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 . 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. 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.