miR-124 Suppresses Pancreatic Ductal Adenocarcinoma Growth by Regulating Monocarboxylate Transporter 1-Mediated Cancer Lactate Metabolism.

BACKGROUND/AIMS: Increasing evidence shows that reprogramming of energy metabolism is a hallmark of cancer. Considering the emergence of microRNAs as crucial modulators of cancer, this study aimed to better understand the molecular mechanisms of miR-124 in regulating glycolysis in human pancreatic cancer. METHODS: RT-PCR was used to investigate the expression of monocarboxylate transporters (MCTs) in pancreatic ductal adenocarcinoma (PDAC) patient samples and the PANC-1 cell line. A public database and immunochemistry were used for comprehensive analysis of MCT1 expression. The targeting of MCT1 by miR-124 was predicted by software and validated for the MCT1 3'-UTR by dual-luciferase reporter analysis. Cell proliferation, apoptosis, migration, xenografting, and the intracellular pH and L-lactate levels were assessed. Hypoxia-inducible factor-α (HIF-1α) and lactate dehydrogenase A (LDH-A) expression levels were determined by RT-PCR and western blotting. RESULTS: MCT1 expression was higher in PDAC tissue than in normal tissue. Inhibition of MCT1 affected lactate metabolism, resulting in a higher intracellular pH and less proliferation of PANC-1 cells. MCT1 was the target gene of miR-124. In in vitro experiments, miR-124 inhibited the glycolytic activity of PANC-1 cells by targeting MCT1, further decreasing the tumor phenotype by increasing the intracellular pH through LDH-A and HIF-1α. In in vivo experiments, overexpression of miR-124 and silencing of MCT1 significantly inhibited tumor growth. CONCLUSION: miR-124 inhibits the progression of PANC-1 by targeting MCT1 in the lactate metabolic pathway. Our findings provide novel evidence for further functional studies of miR-124, which might be useful for future therapeutic approaches to PDAC.

One-half layer pancreaticojejunostomy with the rear wall of the pancreas reinforced: A valuable anastomosis technique.

BACKGROUND: Postoperative pancreatic fistula (POPF) is one of the most common and serious complications after pancreaticoduodenectomy (PD). To effectively reduce the incidence of POPF, we designed a new type of pancreaticojejunostomy (PJ), which was termed one-half layer PJ with the rear wall of the pancreas reinforced. AIM: To explore the clinical application value of this new technique. METHODS: We compared 62 patients who had undergone PD by either the traditional duct-to-mucosa anastomoses or the new one-half layer PJ with the rear wall of the pancreas reinforced method at our hospital from May 2015 to September 2019. All 62 patients were operated by the same surgeon experienced in both procedures. We retrospectively analyzed patient characteristics, perioperative outcomes, and surgical results. RESULTS: There was no significant difference between the two groups in basic information except the postoperative hospital stays, 14.7 ± 5.4 d in the traditional duct-to-mucosa anastomoses group and 12.0 ± 4.2 d in the one-half layer PJ group (P = 0.042). In terms of postoperative complications, the one-half layer PJ group had a lower rate of POPF than the traditional group. The overall number of cases with POPF was 8 (24.2%) in the traditional group and 2 (6.9%) in the one-half layer group (P = 0.017). Additionally, the rate of grades B and C POPF was lower in the one-half layer group (3.4%) compared with that (12.1%) in the traditional group (P = 0.010). One patient died due to hemorrhage caused by severe pancreatic fistula in the traditional group. CONCLUSION: One-half layer PJ with the rear wall of the pancreas reinforced is a safe and feasible procedure that can successfully reduce the rate of POPF. It may be a promising technique for PJ after PD.