Down-regulation of DPP4 by TGF1/miR29a-3p inhibited proliferation and promoted migration of ovarian cancer cells

ObjectiveTo explore the DPP4 expression changes and functions in ovarian cancer (OV), as well as the regulation mechanism for DDP4.MethodsGEPIA2, GSE18520, GSE26712 and UALCAN were used to analyze differences in DPP4 expression between OV tumors and control tissues. Serum DPP4 levels were measured by ELISA. The prognostic values of DPP4 were evaluated using a Kaplan-Meier (KM) plotter. Small interfering RNA was used for DPP4 knockdown in OVCAR-3 and SKOV-3 cells. CCK-8 and scratch healing assays were used to determine the cells' proliferation and migration abilities. Flow cytometry (FCM) was used to detect the cell cycle and apoptosis. A dual-luciferase assay was designed to confirm the regulatory effect of miR-29a-3p on DPP4.ResultsThe expressions of DPP4 mRNA and protein were decreased in OV tumor tissues. Serum DPP4 levels decreased in OV patients. KM plotter analysis showed correlation between high DPP4 expression and a poor prognosis in OV patients. By targeting knockdown of DPP4, we found that OVCAR-3 and SKOV-3 cells' proliferation was inhibited, while cell's migration ability was significantly promoted. FCM analysis showed that DPP4 knockdown induced a decrease in the S phase. Furthermore, DPP4 was shown to be downregulated by miR-29a-3p and TGF beta 1 in OVCAR-3 cells, and miR-29a-3p expression was upregulated by TGF beta 1. The effects of miR-29a-3p and TGF beta 1 on OVCAR-3 cells' biological behaviors were consistent with DPP4 knockdown.ConclusionDPP4 was downregulated in OV patients. DPP4 knockdown significantly inhibited OVCAR-3 and SKOV-3 cell proliferation and promoted cell migration. DDP4 can be downregulated by TGF beta 1 through the upregulation of miR-29a-3p in OV cells.