BACKGROUND An increasing number of studies have focused on the role of cellular metabolism in the development of colorectal cancer(CRC).However,no work is currently available to synthesize the field through bibliometr...BACKGROUND An increasing number of studies have focused on the role of cellular metabolism in the development of colorectal cancer(CRC).However,no work is currently available to synthesize the field through bibliometrics.AIM To analyze the development in the field of“glucose metabolism”(GM),“amino acid metabolism”(AM),“lipid metabolism”(LM),and“nucleotide metabolism”(NM)in CRC by visualization.METHODS Articles within the abovementioned areas of GM,AM,LM and NM in CRC,which were published from January 1,1991,to December 31,2022,are retrieved from the Web of Science Core Collection and analyzed by CiteSpace 6.2.R4 and VOSviewer 1.6.19.RESULTS The field of LM in CRC presented the largest number of annual publications and the fastest increase in the last decade compared with the other three fields.Meanwhile,China and the United States were two of the most prominent contri-butors in these four areas.In addition,Gang Wang,Wei Jia,Maria Notar-nicola,and Cornelia Ulrich ranked first in publication numbers,while Jing-Yuan Fang,Senji Hirasawa,Wei Jia,and Charles Fuchs were the most cited authors on average in these four fields,respectively.“Gut microbiota”and“epithelial-mesenchymal transition”emerged as the newest burst words in GM,“gut microbiota”was the latest outburst word in AM,“metastasis”,“tumor microenvironment”,“fatty acid metabolism”,and“metabolic reprogramming”were the up-to-date outbreaking words in LM,while“epithelial-mesenchymal transition”and“apoptosis”were the most recently occurring words in NM.CONCLUSION Research in“cellular metabolism in CRC”is all the rage at the moment,and researchers are particularly interested in exploring the mechanism to explain the metabolic alterations in CRC.Targeting metabolic vulnerability appears to be a promising direction in CRC therapy.展开更多
Emerging evidence indicates that metabolism reprogramming plays an important role in cancer progression.RNAbinding protein nucleolin(NCL)was reported to function as an important oncogenic factor in multiple cancer typ...Emerging evidence indicates that metabolism reprogramming plays an important role in cancer progression.RNAbinding protein nucleolin(NCL)was reported to function as an important oncogenic factor in multiple cancer types.However,the role and mechanism of NCL in cancer metabolism are unknown.In this study,we found that NCL directly interacted with hnRNPA1 and promoted CRC cell proliferation by enhancing aerobic glycolysis.Mechanistically,NCL bound PKM pre-mRNA and increased hnRNPA1-mediated PKM alternative splicing,resulting in increased PKM2 expression and tumor growth.A seed-mediated growth approach was used to synthesize gold nanostars(GNS),which were further modified with aptamer AS1411(an NCL ligand),GE11(an EGFR ligand),and nuclear localization signal to obtain functionalized nanoparticles(GNSAS1411-GE11).GNS-AS1411-GE11 efficiently enter the nucleus of CRC cells and blocked the glycolysis-promoting effects of NCL,inhibiting the growth of CRC xenograft.Targeting NCL is a promising strategy for treating CRC.展开更多
The IL-6-STAT3 axis is critically involved in inflammation-associated carcinogenesis(IAC).How this axis is regulated to modulate IAC remains unknown.Here,we show that the plasma membrane-associated E3 ubiquitin ligase...The IL-6-STAT3 axis is critically involved in inflammation-associated carcinogenesis(IAC).How this axis is regulated to modulate IAC remains unknown.Here,we show that the plasma membrane-associated E3 ubiquitin ligase MARCH3 negatively regulates STAT3 activation triggered by IL-6,as well as another IL-6 subfamily member,Oncostatin M(OSM).MARCH3 is associated with the IL-6 receptorα-chain(IL-6Rα)and its coreceptor gp130.Biochemical experiments indicated that MARCH3 mediates the polyubiquitination of IL-6Rαat K401 and gp130 at K849 following IL-6 stimulation,leading to their translocation to and degradation in lysosomes.MARCH3 deficiency increases IL-6-and OSM-triggered activation of STAT3 and induction of downstream effector genes in various cell types.MARCH3 deficiency enhances dextran sulfate sodium(DSS)-induced STAT3 activation,increases the expression of inflammatory cytokines,and exacerbates colitis,as well as azoxymethane(AOM)/DSS-induced colitis-associated cancer in mice.In addition,MARCH3 is downregulated in human colorectal cancer tissues and associated with poor survival across different cancer types.Our findings suggest that MARCH3 is a pivotal negative regulator of IL-6-induced STAT3 activation,inflammation,and inflammation-associated carcinogenesis.展开更多
基金National Natural Science Foundation of China,No.82173063 and No.81972220Wuxi Taihu Lake Talent Plan Supporting for Leading Talents in Medical and Health Profession+2 种基金Wuxi Medical Key Discipline,No.ZDXK2021002China Postdoctoral Science Foundation,No.2022M711370Postgraduate Research&Practice Innovation Program of Jiangsu Province,No.KYCX23_2573.
文摘BACKGROUND An increasing number of studies have focused on the role of cellular metabolism in the development of colorectal cancer(CRC).However,no work is currently available to synthesize the field through bibliometrics.AIM To analyze the development in the field of“glucose metabolism”(GM),“amino acid metabolism”(AM),“lipid metabolism”(LM),and“nucleotide metabolism”(NM)in CRC by visualization.METHODS Articles within the abovementioned areas of GM,AM,LM and NM in CRC,which were published from January 1,1991,to December 31,2022,are retrieved from the Web of Science Core Collection and analyzed by CiteSpace 6.2.R4 and VOSviewer 1.6.19.RESULTS The field of LM in CRC presented the largest number of annual publications and the fastest increase in the last decade compared with the other three fields.Meanwhile,China and the United States were two of the most prominent contri-butors in these four areas.In addition,Gang Wang,Wei Jia,Maria Notar-nicola,and Cornelia Ulrich ranked first in publication numbers,while Jing-Yuan Fang,Senji Hirasawa,Wei Jia,and Charles Fuchs were the most cited authors on average in these four fields,respectively.“Gut microbiota”and“epithelial-mesenchymal transition”emerged as the newest burst words in GM,“gut microbiota”was the latest outburst word in AM,“metastasis”,“tumor microenvironment”,“fatty acid metabolism”,and“metabolic reprogramming”were the up-to-date outbreaking words in LM,while“epithelial-mesenchymal transition”and“apoptosis”were the most recently occurring words in NM.CONCLUSION Research in“cellular metabolism in CRC”is all the rage at the moment,and researchers are particularly interested in exploring the mechanism to explain the metabolic alterations in CRC.Targeting metabolic vulnerability appears to be a promising direction in CRC therapy.
基金supported by the National Natural Science Foundation of China(No.81802462,81972220,and 82173063)the Natural Science Foundation of Jiangsu Province,China(No.BK20180618 and BE2019632)+3 种基金Wuxi Taihu Lake Talent Plan,and Wuxi Medical Key Discipline(China)(No.ZDXK2021002)China Postdoctoral Science Foundation(No.2020M681493)Postdoctoral Science Foundation of Jiangsu Province,China(No.2020Z050)Fundamental Research Funds for the Central Universities(China)(No.JUSRP11952).
文摘Emerging evidence indicates that metabolism reprogramming plays an important role in cancer progression.RNAbinding protein nucleolin(NCL)was reported to function as an important oncogenic factor in multiple cancer types.However,the role and mechanism of NCL in cancer metabolism are unknown.In this study,we found that NCL directly interacted with hnRNPA1 and promoted CRC cell proliferation by enhancing aerobic glycolysis.Mechanistically,NCL bound PKM pre-mRNA and increased hnRNPA1-mediated PKM alternative splicing,resulting in increased PKM2 expression and tumor growth.A seed-mediated growth approach was used to synthesize gold nanostars(GNS),which were further modified with aptamer AS1411(an NCL ligand),GE11(an EGFR ligand),and nuclear localization signal to obtain functionalized nanoparticles(GNSAS1411-GE11).GNS-AS1411-GE11 efficiently enter the nucleus of CRC cells and blocked the glycolysis-promoting effects of NCL,inhibiting the growth of CRC xenograft.Targeting NCL is a promising strategy for treating CRC.
基金This work was supported by grants from the National Key R&D Program of China(2017YFA0505800)the National Natural Science Foundation of China(31630045,31830024,31900556,and 32070775)+2 种基金the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-071)the National Postdoctoral Program for Innovative Talents(BX20190255)the China Postdoctoral Science Foundation(2019M662706).
文摘The IL-6-STAT3 axis is critically involved in inflammation-associated carcinogenesis(IAC).How this axis is regulated to modulate IAC remains unknown.Here,we show that the plasma membrane-associated E3 ubiquitin ligase MARCH3 negatively regulates STAT3 activation triggered by IL-6,as well as another IL-6 subfamily member,Oncostatin M(OSM).MARCH3 is associated with the IL-6 receptorα-chain(IL-6Rα)and its coreceptor gp130.Biochemical experiments indicated that MARCH3 mediates the polyubiquitination of IL-6Rαat K401 and gp130 at K849 following IL-6 stimulation,leading to their translocation to and degradation in lysosomes.MARCH3 deficiency increases IL-6-and OSM-triggered activation of STAT3 and induction of downstream effector genes in various cell types.MARCH3 deficiency enhances dextran sulfate sodium(DSS)-induced STAT3 activation,increases the expression of inflammatory cytokines,and exacerbates colitis,as well as azoxymethane(AOM)/DSS-induced colitis-associated cancer in mice.In addition,MARCH3 is downregulated in human colorectal cancer tissues and associated with poor survival across different cancer types.Our findings suggest that MARCH3 is a pivotal negative regulator of IL-6-induced STAT3 activation,inflammation,and inflammation-associated carcinogenesis.
