Objectives:Gastric cancer(GC)is among the most prevalent malignancies worldwide,ranking as the fifth most common cancer and the fifth leading cause of cancer-related mortality.This study intends to investigate how Inh...Objectives:Gastric cancer(GC)is among the most prevalent malignancies worldwide,ranking as the fifth most common cancer and the fifth leading cause of cancer-related mortality.This study intends to investigate how Inhibin subunit beta A(INHBA)promotes the progression of GC by activating the mitogen-activated protein kinase(MAPK)signaling pathway via targeting Integrin alpha-6(ITGA6).Methods:Quantitative reverse transcription-Polymerase Chain Reaction(qRT-PCR)and Immunohistochemistry(IHC)were utilised to validate the expression levels of INHBA in GC,which were subsequently correlated with the clinicopathological factors and outcomes.Cellular and animal studies were conducted to ascertain the role of INHBA in GC.RNA-sequencing(RNA-seq)and bioinformatics analysis were used to screen for the downstream target and pathway of INHBA,with Co-immunoprecipitation(Co-IP),Co-Immunofluorescent(Co-IF),Western blot(WB)and Rescue experiments validating their mechanisms of action in GC.Results:IHC and qRT-PCR analysis confirmed that GC tissues exhibited higher INHBA expression than adjacent noncancerous tissues.This elevated INHBA expression was found to be significantly associated with the incidence of tumor lesions,lymph node metastasis,and progression to higher TNM stages.Functional experiments showed that INHBA promoted GC cell proliferation and enhanced their migration and invasion in vitro while inhibiting apoptosis.Animal studies results indicated that INHBA overexpression promoted tumor growth and increased tumor weight and volume.Through a series of experiments,including RNA-seq,Co-IP,Co-IF,WB,and rescue assays,this study demonstrated that INHBA promotes GC progression by targeting ITGA6 to regulate the MAPK signaling pathway.Conclusions:INHBA/ITGA6/MAPK axis can provide new insights into GC therapy.Targeted INHBA inhibition holds promise as a therapeutic approach for GC treatment.展开更多
Objective To explore the correlation between IT-GA6 gene ( rs12621278, G ) , MSMB gene ( rs10993994,T) ,chromosome 8q24 9 ( rs10086908, T) and prostate cancer ( PCa) in Beijing residents,and to explore the correlation...Objective To explore the correlation between IT-GA6 gene ( rs12621278, G ) , MSMB gene ( rs10993994,T) ,chromosome 8q24 9 ( rs10086908, T) and prostate cancer ( PCa) in Beijing residents,and to explore the correlation between genotype and pheno-展开更多
Fucosyltransferase 8(Fut8)and core fucosylation play critical roles in regulating various biological processes,including immune response,signal transduction,proteasomal degradation,and energy metabolism.However,the fu...Fucosyltransferase 8(Fut8)and core fucosylation play critical roles in regulating various biological processes,including immune response,signal transduction,proteasomal degradation,and energy metabolism.However,the function and underlying mechanism of Fut8 and core fucosylation in regulating adult neurogenesis remains unknown.We have shown that Fut8 and core fucosylation display dynamic features during the differentiation of adult neural stem/progenitor cells(aNSPCs)and postnatal brain development.Fut8 depletion reduces the proliferation of a NSPCs and inhibits neuronal differentiation of aNSPCs in vitro and in vivo,respectively.Additionally,Fut8 deficiency impairs learning and memory in mice.Mechanistically,Fut8 directly interacts with integrinα6(Itga6),an upstream regulator of the PI3kAkt signaling pathway,and catalyzes core fucosylation of Itga6.Deletion of Fut8 enhances the ubiquitination of Itga6 by promoting the binding of ubiquitin ligase Trim21 to Itga6.Low levels of Itga6 inhibit the activity of the PI3K/Akt signaling pathway.Moreover,the Akt agonist SC79 can rescue neurogenic and behavioral deficits caused by Fut8 deficiency.In summary,our study uncovers an essential function of Fut8 and core fucosylation in regulating adult neurogenesis and sheds light on the underlying mechanisms.展开更多
基金funded by Medical Science Foundation of Hebei University 2024B03Hebei Provincial Government-funded Provincial Medical Excellent Talent Project ZF2023025,ZF2024134,ZF2025045,ZF2025048,and ZF2025051+3 种基金Hebei Natural Science Foundation H2022206292,H2024206140Key R&D Program of Hebei Province 223777103D and 223777113DHebei Province County General Hospital Appropriate Health Technology Promotion Project 20220018other projects of Hebei Province SGH201501.
文摘Objectives:Gastric cancer(GC)is among the most prevalent malignancies worldwide,ranking as the fifth most common cancer and the fifth leading cause of cancer-related mortality.This study intends to investigate how Inhibin subunit beta A(INHBA)promotes the progression of GC by activating the mitogen-activated protein kinase(MAPK)signaling pathway via targeting Integrin alpha-6(ITGA6).Methods:Quantitative reverse transcription-Polymerase Chain Reaction(qRT-PCR)and Immunohistochemistry(IHC)were utilised to validate the expression levels of INHBA in GC,which were subsequently correlated with the clinicopathological factors and outcomes.Cellular and animal studies were conducted to ascertain the role of INHBA in GC.RNA-sequencing(RNA-seq)and bioinformatics analysis were used to screen for the downstream target and pathway of INHBA,with Co-immunoprecipitation(Co-IP),Co-Immunofluorescent(Co-IF),Western blot(WB)and Rescue experiments validating their mechanisms of action in GC.Results:IHC and qRT-PCR analysis confirmed that GC tissues exhibited higher INHBA expression than adjacent noncancerous tissues.This elevated INHBA expression was found to be significantly associated with the incidence of tumor lesions,lymph node metastasis,and progression to higher TNM stages.Functional experiments showed that INHBA promoted GC cell proliferation and enhanced their migration and invasion in vitro while inhibiting apoptosis.Animal studies results indicated that INHBA overexpression promoted tumor growth and increased tumor weight and volume.Through a series of experiments,including RNA-seq,Co-IP,Co-IF,WB,and rescue assays,this study demonstrated that INHBA promotes GC progression by targeting ITGA6 to regulate the MAPK signaling pathway.Conclusions:INHBA/ITGA6/MAPK axis can provide new insights into GC therapy.Targeted INHBA inhibition holds promise as a therapeutic approach for GC treatment.
文摘Objective To explore the correlation between IT-GA6 gene ( rs12621278, G ) , MSMB gene ( rs10993994,T) ,chromosome 8q24 9 ( rs10086908, T) and prostate cancer ( PCa) in Beijing residents,and to explore the correlation between genotype and pheno-
基金supported in part by the National Natural Science Foundation of China(92049108,82371182)Central Guiding Fund for Local Science and Technology Development Projects(2023ZY1058)the National Key Research and Development Program of China(2017YFE0196600)。
文摘Fucosyltransferase 8(Fut8)and core fucosylation play critical roles in regulating various biological processes,including immune response,signal transduction,proteasomal degradation,and energy metabolism.However,the function and underlying mechanism of Fut8 and core fucosylation in regulating adult neurogenesis remains unknown.We have shown that Fut8 and core fucosylation display dynamic features during the differentiation of adult neural stem/progenitor cells(aNSPCs)and postnatal brain development.Fut8 depletion reduces the proliferation of a NSPCs and inhibits neuronal differentiation of aNSPCs in vitro and in vivo,respectively.Additionally,Fut8 deficiency impairs learning and memory in mice.Mechanistically,Fut8 directly interacts with integrinα6(Itga6),an upstream regulator of the PI3kAkt signaling pathway,and catalyzes core fucosylation of Itga6.Deletion of Fut8 enhances the ubiquitination of Itga6 by promoting the binding of ubiquitin ligase Trim21 to Itga6.Low levels of Itga6 inhibit the activity of the PI3K/Akt signaling pathway.Moreover,the Akt agonist SC79 can rescue neurogenic and behavioral deficits caused by Fut8 deficiency.In summary,our study uncovers an essential function of Fut8 and core fucosylation in regulating adult neurogenesis and sheds light on the underlying mechanisms.
