Cancer multidrug resistance(MDR)impairs the therapeutic efficacy of various chemotherapeutics.Novel approaches,particularly the development of MDR reversal agents,are critically needed to address this challenge.This s...Cancer multidrug resistance(MDR)impairs the therapeutic efficacy of various chemotherapeutics.Novel approaches,particularly the development of MDR reversal agents,are critically needed to address this challenge.This study demonstrates that tenacissoside I(TI),a compound isolated from Marsdenia tenacissima(Roxb.)Wight et Arn,traditionally used in clinical practice as an ethnic medicine for cancer treatment,exhibits significant MDR reversal effects in ABCB1-mediated MDR cancer cells.TI reversed the resistance of SW620/AD300 and KBV200 cells to doxorubicin(DOX)and paclitaxel(PAC)by downregulating ABCB1 expression and reducing ABCB1 drug transport function.Mechanistically,protein arginine methyltransferase 1(PRMT1),whose expression correlates with poor prognosis and shows positive association with both ABCB1 and EGFR expressions in tumor tissues,was differentially expressed in TI-treated SW620/AD300 cells.SW620/AD300 and KBV200 cells exhibited elevated levels of EGFR asymmetric dimethylarginine(aDMA)and enhanced PRMT1-EGFR interaction compared to their parental cells.Moreover,TI-induced PRMT1 downregulation impaired PRMT1-mediated aDMA of EGFR,PRMT1-EGFR interaction,and EGFR downstream signaling in SW620/AD300 and KBV200 cells.These effects were significantly reversed by PRMT1 overexpression.Additionally,TI demonstrated resistance reversal to PAC in xenograft models without detectable toxicities.This study establishes TI's MDR reversal effect in ABCB1-mediated MDR human cancer cells through inhibition of PRMT1-mediated aDMA of EGFR,suggesting TI's potential as an MDR modulator for improving chemotherapy outcomes.展开更多
[Objective] The aim of experiment was to lay molecular foundation for studying maturity mechanism of banana after harvest. [Method] The combined method of suppressing subtractive hybridization and cDNA micro-array wer...[Objective] The aim of experiment was to lay molecular foundation for studying maturity mechanism of banana after harvest. [Method] The combined method of suppressing subtractive hybridization and cDNA micro-array were used to obtain cDNA segment of one PRMT gene in banana and the whole cDNA sequence of the gene was cloned.The bioinformatics analysis was operated on it,in addition, the expression profile analysis was conducted in different organs and different mature periods of banana.[Result] The whole length of cDNA in MaPRMT1 was 1 158 bp and possessed a complete open reading frame,which could encode 385 amino acids.It had high homology with PRMT in plant,containing one Methyltransf_1 domain.The MaPRMT1 gene was expressed in root,stem,leaf and fruit of banana and the expression levels in stem and leaf were relatively high.As the increase of days after harvest,the expression level declined gradually,however it reached maximum when ethylene release was biggest,then it declined.[Conclusion] MaPRMT1 belonged to the first kind of arginine methyltransferase and it was expressed differently in different organs and fruits at different mature periods.展开更多
Long-read sequencing with nanopore technology has been widely utilized for the identification of the full-length sequence of RNA molecules."It is especially suitable for the identification of circular RNAs(circRN...Long-read sequencing with nanopore technology has been widely utilized for the identification of the full-length sequence of RNA molecules."It is especially suitable for the identification of circular RNAs(circRNAs),which are regulatory molecules that are regarded as promising non-invasive biomarkers for various human malignancies,including breast cancer.2 The impact of circRNAs derived from the protein arginine methyltransferase 1(PRMT1)gene has not been clarified yet,even though the effect of PRMT1-mediated methylation on breast cancer cell characteristics has been well established.展开更多
Neutrophils are mobilized and recruited to the injured heart after myocardial infarction,and neutrophil count has been clinically implicated to be associated with coronary disease severity.Histidine decarboxylase(HDC)...Neutrophils are mobilized and recruited to the injured heart after myocardial infarction,and neutrophil count has been clinically implicated to be associated with coronary disease severity.Histidine decarboxylase(HDC)has been implicated in regulating reactive oxidative species(ROS)and the differentiation of myeloid cells.However,the effect of HDC on neutrophils after myocardial infarction remains unclear.Here,we found that neutrophils were disorderly recruited into the ischemic injured area of the myocardium of Hdc deficiency(Hdc^(−/−))mice.Moreover,Hdc deficiency led to attenuated adhesion but enhanced migration and augmented ROS/neutrophil extracellular traps(NETs)production in neutrophils.Hdc^(−/−)mouse-derived NETs promoted cardiomyocyte death and cardiac fibroblast proliferation/migration.Furthermore,protein arginine methyltransferase 1(PRMT1)was increased in Hdc^(−/−)mouse-derived neutrophils but decreased with exogenous histamine treatment.Its expression could be rescued by blocking histamine receptor 1(H1R),inhibiting ATP synthesis or reducing SWItch/sucrose non fermentable(SWI/SNF)chromatin remodeling complex.Accordingly,histamine or MS023 treatment could decrease ROS and NETs ex vivo,and ameliorated cardiac function and fibrosis,along with the reduced NETs in plasma in vivo.Together,our findings unveil the role of HDC in NETosis by histamine–H1R–ATP–SWI/SNF–PRMT1–ROS signaling and provide new biomarkers and targets for identifying and tuning the detrimental immune state in cardiovascular disease.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82274211 and 82474190)the Natural Science Foundation of Tianjin(Nos.24JCZDJC00120 and 24PTLYHZ00280)Liaoning Provincial Department of Education Basic Research Projects for Higher Education Institutions(No.LJ212510163021)。
文摘Cancer multidrug resistance(MDR)impairs the therapeutic efficacy of various chemotherapeutics.Novel approaches,particularly the development of MDR reversal agents,are critically needed to address this challenge.This study demonstrates that tenacissoside I(TI),a compound isolated from Marsdenia tenacissima(Roxb.)Wight et Arn,traditionally used in clinical practice as an ethnic medicine for cancer treatment,exhibits significant MDR reversal effects in ABCB1-mediated MDR cancer cells.TI reversed the resistance of SW620/AD300 and KBV200 cells to doxorubicin(DOX)and paclitaxel(PAC)by downregulating ABCB1 expression and reducing ABCB1 drug transport function.Mechanistically,protein arginine methyltransferase 1(PRMT1),whose expression correlates with poor prognosis and shows positive association with both ABCB1 and EGFR expressions in tumor tissues,was differentially expressed in TI-treated SW620/AD300 cells.SW620/AD300 and KBV200 cells exhibited elevated levels of EGFR asymmetric dimethylarginine(aDMA)and enhanced PRMT1-EGFR interaction compared to their parental cells.Moreover,TI-induced PRMT1 downregulation impaired PRMT1-mediated aDMA of EGFR,PRMT1-EGFR interaction,and EGFR downstream signaling in SW620/AD300 and KBV200 cells.These effects were significantly reversed by PRMT1 overexpression.Additionally,TI demonstrated resistance reversal to PAC in xenograft models without detectable toxicities.This study establishes TI's MDR reversal effect in ABCB1-mediated MDR human cancer cells through inhibition of PRMT1-mediated aDMA of EGFR,suggesting TI's potential as an MDR modulator for improving chemotherapy outcomes.
文摘[Objective] The aim of experiment was to lay molecular foundation for studying maturity mechanism of banana after harvest. [Method] The combined method of suppressing subtractive hybridization and cDNA micro-array were used to obtain cDNA segment of one PRMT gene in banana and the whole cDNA sequence of the gene was cloned.The bioinformatics analysis was operated on it,in addition, the expression profile analysis was conducted in different organs and different mature periods of banana.[Result] The whole length of cDNA in MaPRMT1 was 1 158 bp and possessed a complete open reading frame,which could encode 385 amino acids.It had high homology with PRMT in plant,containing one Methyltransf_1 domain.The MaPRMT1 gene was expressed in root,stem,leaf and fruit of banana and the expression levels in stem and leaf were relatively high.As the increase of days after harvest,the expression level declined gradually,however it reached maximum when ethylene release was biggest,then it declined.[Conclusion] MaPRMT1 belonged to the first kind of arginine methyltransferase and it was expressed differently in different organs and fruits at different mature periods.
文摘Long-read sequencing with nanopore technology has been widely utilized for the identification of the full-length sequence of RNA molecules."It is especially suitable for the identification of circular RNAs(circRNAs),which are regulatory molecules that are regarded as promising non-invasive biomarkers for various human malignancies,including breast cancer.2 The impact of circRNAs derived from the protein arginine methyltransferase 1(PRMT1)gene has not been clarified yet,even though the effect of PRMT1-mediated methylation on breast cancer cell characteristics has been well established.
基金This study was supported by grants from the National Key Research and Development Plan(2016YFC1101102,China)the National Natural Science Foundation of China(81521001 and 81500262)+1 种基金the Basic Research Project of Shanghai Committee of Science and Technology(19JC1411400,China)the Laboratory Animal Science Foundation of Shanghai Committee of Science and Technology(19140902000,China).
文摘Neutrophils are mobilized and recruited to the injured heart after myocardial infarction,and neutrophil count has been clinically implicated to be associated with coronary disease severity.Histidine decarboxylase(HDC)has been implicated in regulating reactive oxidative species(ROS)and the differentiation of myeloid cells.However,the effect of HDC on neutrophils after myocardial infarction remains unclear.Here,we found that neutrophils were disorderly recruited into the ischemic injured area of the myocardium of Hdc deficiency(Hdc^(−/−))mice.Moreover,Hdc deficiency led to attenuated adhesion but enhanced migration and augmented ROS/neutrophil extracellular traps(NETs)production in neutrophils.Hdc^(−/−)mouse-derived NETs promoted cardiomyocyte death and cardiac fibroblast proliferation/migration.Furthermore,protein arginine methyltransferase 1(PRMT1)was increased in Hdc^(−/−)mouse-derived neutrophils but decreased with exogenous histamine treatment.Its expression could be rescued by blocking histamine receptor 1(H1R),inhibiting ATP synthesis or reducing SWItch/sucrose non fermentable(SWI/SNF)chromatin remodeling complex.Accordingly,histamine or MS023 treatment could decrease ROS and NETs ex vivo,and ameliorated cardiac function and fibrosis,along with the reduced NETs in plasma in vivo.Together,our findings unveil the role of HDC in NETosis by histamine–H1R–ATP–SWI/SNF–PRMT1–ROS signaling and provide new biomarkers and targets for identifying and tuning the detrimental immune state in cardiovascular disease.
