RESUMO
Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.
RESUMO
Objective To observe the effect of Shoutaiwan on the expression ofα-enolase in the decidua tissue of recurrent abortion mice. Methods The abortion-prone CBA/J × DBA/2 matings were established as the model of recurrent abortion and the nonabortion-prone CBA/J×BALB/C matings were used as the model of normal pregnancy. The model of recurrent abortion CBA/J × DBA/2 of pregnant mice were randomly divided into model group and Shoutaiwan high-, medium-, low-dose groups, pregnant mice of every group were orally administrated in different doses. On the 14th day of pregnancy, the mice were killed. The expression ofα-enolase was detected by using immunohistochemical method and Western Blot. Results α-enolase expression in the model group was significantly higher than the normal pregnancy group (P0.05). Conclusion Shoutaiwan could down-regulate the expression ofα-enolase in the decidua tissues of recurrent abortion mice, which may be one of its mechanisms of preventing miscarriage.
RESUMO
Objective To explore the mechanism action of Shoutai Pill in the embryo from the molecular level. Methods The model of normal pregnancy was established with the model of recurrent abortion CBA/J ×DBA/2. The recurrent abortion model CBA/J×DBA/2 in pregnant mice were randomly divided into model group, high-, medium-, low-dose group of Shoutai Pill. From the first day of gestation, mice were given medicine by gavage for 14 d, and then sacrificed. Immunohistochemistry was used to detect differences in protein HSP27,α-enolase, transferrin, annexin A2 protein expression. Results Compared with normal group, decidual HSP27 and α-enolase expression of model group increased significantly, the expression of transferrin and annexin A2 was significantly decreased, with significant differences (P0.05). Conclusion Through the protein expression, Shoutai Pill achieves the maintenance of pregnancy, reducing the rate of embryo resorption, which may be one of the mechanisms of Shoutai Pill preventing miscarriage effect.
