Alterations in Glucose Metabolism Due to Decreased Expression of Heterogeneous Nuclear Ribonucleoprotein M in Pancreatic Ductal Adenocarcinoma

SIMPLE SUMMARY: Pancreatic cancer has one of the worst prognoses when compared to those of other cancer subtypes. One of the reasons is the resistance of this tumor to the hypovascular environment (an environment with low blood flow and low supply of oxygen and nutrients (especially glucose)). However, the detailed mechanism remains elusive. Recently, it has been reported that heterogeneous ribonuclear protein M (HNRNPM) is a splicing factor associated with malignant tumors. Thus, in this study, we investigated the expression and effects of HNRNPM in pancreatic ductal adenocarcinoma (PDA). We revealed that HNRNPM was highly expressed in pancreatic tissues but expression decreased in PDA tissues. Furthermore, we found that knockdown of HNRNPM protein expression under low-glucose conditions altered glucose metabolism and prolonged cell survival by suppressing glucose consumption. These results suggest that reduced expression of HNRNPM in PDAs may be involved in adaptation to a hypovascular environment, and that therapeutic agents for this target may lead to improved prognosis for pancreatic cancer. ABSTRACT: The prognosis of pancreatic cancer is considerably worse than that of other cancers, as early detection of pancreatic cancer is difficult and due to its hypovascular environment, which involves low blood flow and a low supply of oxygen and nutrients. Moreover, pancreatic cancer demonstrates a mechanism that allows it to survive in a hypovascular environment. However, the detailed mechanism remains elusive. Recently, it has been reported that heterogeneous ribonuclear protein M (HNRNPM) is a splicing factor associated with malignant tumors. Thus, in this study, we investigated the expression and effects of HNRNPM in pancreatic ductal adenocarcinoma (PDA). We observed that HNRNPM expression, which is highly expressed in pancreatic tissues, was reduced in PDA tissues. Additionally, knockdown of HNRNPM under low-glucose conditions that mimic a hypovascular environment was shown to alter glucose metabolism and prolong cell survival by suppressing glucose consumption. These results suggest that the decreased expression of HNRNPM in PDA may be involved in its adaptation to a hypovascular environment.