J Cancer 2017; 8(14):2854-2865. doi:10.7150/jca.18931
MicroRNA-216b-5p Functions as a Tumor-suppressive RNA by Targeting TPT1 in Pancreatic Cancer Cells
Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
* These two authors contributed equally to this work
You Y, Tan J, Gong Y, Dai H, Chen H, Xu X, Yang A, Zhang Y, Bie P. MicroRNA-216b-5p Functions as a Tumor-suppressive RNA by Targeting TPT1 in Pancreatic Cancer Cells. J Cancer 2017; 8(14):2854-2865. doi:10.7150/jca.18931. Available from http://www.jcancer.org/v08p2854.htm
MicroRNAs (miRNAs) are increasingly recognized as being involved in pancreatic cancer progression by directly regulating the expression of their targets. In this study, we showed that miR-216b-5p expression was significantly decreased in pancreatic cancer tissues and cell lines. In addition, low miR-216b-5p expression was significantly associated with large tumor size and advanced TNM stage. Meanwhile, both Kaplan-Meier and multivariate survival analysis showed that decreased miR-216b-5p expression was associated with overall survival. miR-216b-5p over-expression repressed pancreatic cancer cell proliferation and induced cell cycle arrest and cell apoptosis in vitro and inhibited tumorigenesis in vivo. The translationally controlled tumor protein (TPT1) was identified as a novel direct target of miR-216b-5p. miR-216b-5p up-regulation suppressed TPT1 expression. Moreover, TPT1 mRNA expression levels were increased in pancreatic cancer tissues, and were inversely correlated with miR-216b-5p expression. TPT1 down-regulation had similar effects as miR-216b-5p up-regulation on pancreatic cancer cell progression. The restoration of TPT1 reversed the effect of miR-216b-5p on pancreatic cancer cell progression. Furthermore, we found that miR-216b-5p up-regulation suppressed Pim-3, Cyclin B1, p-Bad and Bcl-xL protein expression. However, the effect of miR-216b-5p up-regulation was partly reversed by TPT1 up-regulation in vitro. Taken together, our findings suggested that miR-216b-5p functions as a potential tumor suppressor by regulating TPT1 in pancreatic cancer cells, and it may represent a potential therapeutic target for patients with pancreatic cancer.
Keywords: miR-216b-5p, TPT1, pancreatic cancer, cell cycle.