The nucleophosmin (NPM1) activates cancer development and progression in many malignant tumors. However, the regulatory role and underlying mechanisms of NPM1 in pancreatic cancer are unknown. In this study, we showed that NPM1 was up-regulated in PDAC, which indicated a poor prognosis. We also identified NPM1could stimulate aerobic glycolysis and repress fructose-1, 6-bisphosphatase 1 (FBP1) in pancreatic cancer cells. Restoring FBP1 expression partially reversed the tumor-promoting effects of NPM1, while the loss of FBP1 in PDAC tissues was indicative of a poorer prognosis. In sum, NPM1 promotes aerobic glycolysis and tumor progression in patients with pancreatic cancer by inhibiting FBP1.

The members of the miR-17-92 cluster are upregulated in various cancers and function as a cluster of oncogenic miRNA. Our study characterized a new function of miR-17-5p, a member of the miR-17-92 cluster, in regulating cell proliferation in pancreatic cancer. Our results indicate that miR-17-5p was up-regulated in pancreatic adenocarcinoma and directly targeted the retinoblastoma-like protein 2 (RBL2), a tumor suppressor belonging to the Rb family. High levels of miR-17-5p and low levels of RBL2 were associated with poor prognosis. RBL2 interacted with the transcription factor E2F4 and bound to the promoter regions of the E2F target genes. Disruption of the RBL2/E2F4 complex by miR-17-5p overexpression shifted the activity of E2F from gene repressing to gene activating, which induced cell cycle entry and proliferation. These results suggest that miR-17-5p promoted proliferation in pancreatic ductal adenocarcinoma cells (PDAC), and altered cell cycle profiles in vivo and in vitro, by disrupting the RBL2/E2F4-associated gene repressing complexes via direct targeting of RBL2. The new regulatory network, involving miR-17-5p and RBL2, emerges as a new target of PDAC treatment.

BackgroundThe most effective and radical treatment for pancreatic neuroendocrine tumors (PNETs) is surgical resection. Minimally invasive surgery has been increasingly used in pancreatectomy. Initial results in robotic distal pancreatectomy (RDP) have been encouraging. Nonetheless, data comparing outcomes of RDP with those of laparoscopic distal pancreatectomy (LDP) in treating PNETs are rare. The aim of this study was to compare the safety and efficacy of RDP and LDP for PNETs.MethodsFrom September 2010 to January 2017, operative parameters and perioperative outcomes in an initial experience with 43 consecutive patients undergoing RDP were collected and compared with those in 31 patients undergoing LDP.ResultsPatients undergoing RDP and LDP demonstrated equivalent age, sex, ASA score, tumor location and tumor size. Operating time, length of resected pancreas, postoperative length of hospital stay and rates of conversion to open, pancreatic fistula, transfusion and reoperation were not statistically different. Patients in the RDP group were associated with significantly higher overall (79.1 vs. 48.4 %, P = 0.006) and Kimura spleen preservation rates (72.1 vs. 16.1%, P < 0.001) and had reduced risk of excessive blood loss (50 vs. 200mL, P < 0.001). Oncological outcomes in this series were superior for the RDP group with more lymph node harvest for G2 and G3 PNETs (3.5 vs. 2, P = 0.034).ConclusionsBoth RDP and LDP are efficacious and safe methods in treating PNETs located in the body or tail of pancreas. Robotic approach offers advantages with less intraoperative blood loss, higher spleen preservation rate and more lymph node harvest. It may be sensible to choose RDP for patients who fit indications for scheduled spleen preservation.