Retroperitoneal liposarcoma(RLPS)is the main subtype of retroperitoneal soft sarcoma(RSTS)and has a poor prognosis and few treatment options,except for surgery.The proteomic and metabolic profiles of RLPS have remaine...Retroperitoneal liposarcoma(RLPS)is the main subtype of retroperitoneal soft sarcoma(RSTS)and has a poor prognosis and few treatment options,except for surgery.The proteomic and metabolic profiles of RLPS have remained unclear.The aim of our study was to reveal the metabolic profile of RLPS.Here,we performed proteomic analysis(n=10),metabolomic analysis(n=51),and lipidomic analysis(n=50)of retroperitoneal dedifferentiated liposarcoma(RDDLPS)and retroperitoneal well-differentiated liposarcoma(RWDLPS)tissue and paired adjacent adipose tissue obtained during surgery.Data analysis mainly revealed that glycolysis,purine metabolism,pyrimidine metabolism and phospholipid formation were upregulated in both RDDLPS and RWDLPS tissue compared with the adjacent adipose tissue,whereas the tricarboxylic acid(TCA)cycle,lipid absorption and synthesis,fatty acid degradation and biosynthesis,as well as glycine,serine,and threonine metabolism were downregulated.Of particular importance,the glycolytic inhibitor 2-deoxy-D-glucose and pentose phosphate pathway(PPP)inhibitor RRX-001 significantly promoted the antitumor effects of the MDM2 inhibitor RG7112 and CDK4 inhibitor abemaciclib.Our study not only describes the metabolic profiles of RDDLPS and RWDLPS,but also offers potential therapeutic targets and strategies for RLPS.展开更多
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...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-phosphogluconate dehydrogenase(6PGD)and a-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 antitumor effects of cisplatin in lung cancer.Together,this study demonstrates that PRMT6 acts as a posttranslational 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.展开更多
Dear Editor,The nutrition contents of breastmilk directly participate in neonatal immune response.The alternations of the components of breastmilk under the context of viral infection not only reflect the physiologica...Dear Editor,The nutrition contents of breastmilk directly participate in neonatal immune response.The alternations of the components of breastmilk under the context of viral infection not only reflect the physiological changes in mothers but also affect neonatal immunity and metabolism via breastfeeding.Herein,we attempted to answer the important questions whether breastmilk production is affected by COVID-19 and whether breastfeeding is still a safe or recommended operation for COVID-19 puerperant women.展开更多
基金funded by grants from the National Natural Science Foundation of China(No.82272935 to Wengang Li.,Nos.91957120 and 21974114 to Shuhai Lin.)the Scientific Research Foundation for Advanced Talents,Xiang’an Hospital of Xiamen University(No.PM20180917008 to Wengang Li.)+3 种基金Joint laboratory of School of Medicine,Xiamen University-Shanghai Jiangxia Blood Technology Co.Ltd.(No.XDHT2020010C to Wengang Lin and Ye Shen.)the Fundamental Research Funds for the Central Universities(No.20720210001 to Shuhai Lin.)Major Science and Technology Special Project of Fujian Province(No.2022YZ036012 to Shuhai Lin)Natural Science Foundation of Fujian Province(No.2021J01123522 to Zhigang Zheng).
文摘Retroperitoneal liposarcoma(RLPS)is the main subtype of retroperitoneal soft sarcoma(RSTS)and has a poor prognosis and few treatment options,except for surgery.The proteomic and metabolic profiles of RLPS have remained unclear.The aim of our study was to reveal the metabolic profile of RLPS.Here,we performed proteomic analysis(n=10),metabolomic analysis(n=51),and lipidomic analysis(n=50)of retroperitoneal dedifferentiated liposarcoma(RDDLPS)and retroperitoneal well-differentiated liposarcoma(RWDLPS)tissue and paired adjacent adipose tissue obtained during surgery.Data analysis mainly revealed that glycolysis,purine metabolism,pyrimidine metabolism and phospholipid formation were upregulated in both RDDLPS and RWDLPS tissue compared with the adjacent adipose tissue,whereas the tricarboxylic acid(TCA)cycle,lipid absorption and synthesis,fatty acid degradation and biosynthesis,as well as glycine,serine,and threonine metabolism were downregulated.Of particular importance,the glycolytic inhibitor 2-deoxy-D-glucose and pentose phosphate pathway(PPP)inhibitor RRX-001 significantly promoted the antitumor effects of the MDM2 inhibitor RG7112 and CDK4 inhibitor abemaciclib.Our study not only describes the metabolic profiles of RDDLPS and RWDLPS,but also offers potential therapeutic targets and strategies for RLPS.
基金supported by grants from the Natural Science Foundation of Tianjin(21JCZDJC00060,China)the National Nature Science Foundation of China(81973356,91957120,81902826,and 81672781)+4 种基金the Fundamental Research Funds for the Central Universities of Nankai University(3206054,91923101,63213082 and 92122017,China)the State Key Laboratory of Drug Research(SIMM2105KF-08,China)the National Key R&D Program of China(No.2018YFC2002000)the Innovative S&T Projects for Young Researchers of Tianjin Academy of Agricultural Science(grant No.201918,China)the Natural Science Foundation of Tianjin(19JCYBJC29600 and 21JCYBJC00180,China)。
文摘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-phosphogluconate dehydrogenase(6PGD)and a-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 antitumor effects of cisplatin in lung cancer.Together,this study demonstrates that PRMT6 acts as a posttranslational 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.
基金supported by the Strategic Priority Research Program of CAS(XDB29010300 to X.Z.)the National Science and Technology Major Project(2018ZX10101004 to X.Z.)+2 种基金National Natural Science Foundation of China(81873964 to Y.Q.,91957120 to S.-H.L,81971818 and 81772047 to Y.S.,81771605 to Y.Z.,and 31670161 to X.Z.)Grant from the CAS Youth Innovation Promotion Association(2020332 to Y.Q.)the Fundamental Research Funds for the Central Universities(20720200013 to S.-H.L.).
文摘Dear Editor,The nutrition contents of breastmilk directly participate in neonatal immune response.The alternations of the components of breastmilk under the context of viral infection not only reflect the physiological changes in mothers but also affect neonatal immunity and metabolism via breastfeeding.Herein,we attempted to answer the important questions whether breastmilk production is affected by COVID-19 and whether breastfeeding is still a safe or recommended operation for COVID-19 puerperant women.