miR-939-5p Contributes to the Migration and Invasion of Pancreatic Cancer by Targeting ARHGAP4

Objective: Rho GTPase-activating protein 4 (ARHGAP4) is a GTPase-activating protein for the small GTPases of the Rho family that is involved in tumorigenesis. We recently reported that ARHGAP4 can mediate Warburg effect and malignant phenotype of pancreatic cancer. However, the regulation of ARHGAP4 remains unclear. Methods: ARHGAP4 and miR-939-5p expressions in pancreatic cancer tissues and cell lines were measured by real-time PCR or Western blotting. Pancreatic cancer cells were transfected with miR-939-5p inhibitor, miR-939-5p mimic and/or lentivirus expressing ARHGAP4, and the cell viability, invasion and migration were measured by CCK-8 and Transwell assay, respectively. The suppression of ARHGAP4 expression by miR-939-5p was revealed by luciferase reporter assay, real-time PCR or Western blotting. Results: ARHGAP4 expression was decreased, while miR-939-5p was increased in pancreatic cancer tissues compared with adjacent-normal pancreatic tissues. Higher miR-939-5p expression was correlated with advanced pathological stages and poor prognosis of pancreatic cancer patients. miR-939-5p directly targeted ARHGAP4. Either miR-939-5p down-regulation or ARHGAP4 overexpression inhibited viability, invasion and migration of pancreatic cancer cells. However, ARHGAP4 overexpression markedly inhibited the increased viability, migration, and invasion induced by miR-939-5p up-regulation in pancreatic cancer cells. Conclusion: These observations suggested that miR-939-5p regulates the malignant phenotype of pancreatic cancer cells by targeting ARHGAP4, establishing miR-939-5p as a novel regulator of ARHGAP4 with a critical role in tumorigenesis in pancreatic cancer.