BACKGROUND Colon cancer is acknowledged as one of the most common malignancies worldwide,ranking third in United States regarding incidence and mortality.Notably,approximately 40%of colon cancer cases harbor oncogenic...BACKGROUND Colon cancer is acknowledged as one of the most common malignancies worldwide,ranking third in United States regarding incidence and mortality.Notably,approximately 40%of colon cancer cases harbor oncogenic KRAS mutations,resulting in the continuous activation of epidermal growth factor receptor signaling.AIM To investigate the key pathogenic genes in KRAS mutant colon cancer holds considerable importance.METHODS Weighted gene co-expression network analysis,in combination with additional bioinformatics analysis,were conducted to screen the key factors driving the progression of KRAS mutant colon cancer.Meanwhile,various in vitro experiments were also conducted to explore the biological function of transglutaminase 2(TGM2).RESULTS Integrated analysis demonstrated that TGM2 acted as an independent prognostic factor for progression-free survival.Immunohistochemical analysis on tissue microarrays revealed that TGM2 was associated with an elevated probability of perineural invasion in patients with KRAS mutant colon cancer.Additionally,biological roles of the key gene TGM2 was also assessed,suggesting that the downregulation of TGM2 attenuated the proliferation,invasion,and migration of the KRAS mutant colon cancer cell line.CONCLUSION This study underscores the potential significance of TGM2 in the progression of KRAS mutant colon cancer.This insight not only offers a theoretical foundation for therapeutic approaches but also highlights the need for additional clinical trials and fundamental research to support our preliminary findings.展开更多
BACKGROUND Gastric cancer(GC)is a common gastrointestinal malignancy worldwide.Based on cancer-related mortality,the current prevention and treatment strategies for GC still show poor clinical results.Therefore,it is ...BACKGROUND Gastric cancer(GC)is a common gastrointestinal malignancy worldwide.Based on cancer-related mortality,the current prevention and treatment strategies for GC still show poor clinical results.Therefore,it is important to find effective drug treatment targets.AIM To explore the molecular mechanism of 18β-glycyrrhetinic acid(18β-GRA)regulating the miR-345-5p/TGM2 signaling pathway to inhibit the proliferation of GC cells.METHODS CCK-8 assay was used to determine the effect of 18β-GRA on the survival rate of GES-1 cells and AGS and HGC-27 cells.Cell cycle and apoptosis were detected by flow cytometry,cell migration was detected by a wound healing assay,the effect of 18β-GRA on subcutaneous tumor growth in BALB/c nude mice was investigated,and the cell autophagy level was determined by MDC staining.TMT proteomic analysis was used to detect the differentially expressed autophagy-related proteins in GC cells after 18β-GRA intervention,and then the protein-protein interaction was predicted using STRING(https://string-db.org/).MicroRNAs(miRNAs)transcriptome analysis was used to detect the miRNA differential expression profile,and use miRBase(https://www.mirbase/)and TargetScan(https://www.targetscan.org/)to predict the miRNA and complementary binding sites.Quantitative real-time polymerase chain reaction was used to detect the expression level of miRNA in 18β-GRA treated cells,and western blot was used to detect the expression of autophagy related proteins.Finally,the effect of miR-345-5p on GC cells was verified by mir-345-5p overexpression.RESULTS 18β-GRA could inhibit GC cells viability,promote cell apoptosis,block cell cycle,reduce cell wound healing ability,and inhibit the GC cells growth in vivo.MDC staining results showed that 18β-GRA could promote autophagy in GC cells.By TMT proteomic analysis and miRNAs transcriptome analysis,it was concluded that 18β-GRA could down-regulate TGM2 expression and up-regulate miR-345-5p expression in GC cells.Subsequently,we verified that TGM2 is the target of miR-345-5p,and that overexpression of miR-345-5p significantly inhibited the protein expression level of TGM2.Western blot showed that the expression of autophagy-related proteins of TGM2 and p62 was significantly reduced,and LC3II,ULK1 and AMPK expression was significantly increased in GC cells treated with 18β-GRA.Overexpression of miR-345-5p not only inhibited the expression of TGM2,but also inhibited the proliferation of GC cells by promoting cell apoptosis and arresting cell cycle.CONCLUSION 18β-GRA inhibits the proliferation of GC cells and promotes autophagy by regulating the miR-345-5p/TGM2 signaling pathway.展开更多
Nb-RE微合金化TGM2高速钢(%:0.88～0.89C、4.14～4.16Cr、4.73～4.76Mo、6.09～6.12W、1.85～1.86V、0.05～0.10Nb、0.05～0.06RE)由25 t EAF-30 t LF(VD,加Nb-RE)-1 t ESR工艺冶炼。试验结果表明,经Nb-RE微合金化后,TGM2高速钢Φ96 mm...Nb-RE微合金化TGM2高速钢(%:0.88～0.89C、4.14～4.16Cr、4.73～4.76Mo、6.09～6.12W、1.85～1.86V、0.05～0.10Nb、0.05～0.06RE)由25 t EAF-30 t LF(VD,加Nb-RE)-1 t ESR工艺冶炼。试验结果表明,经Nb-RE微合金化后,TGM2高速钢Φ96 mm材淬火晶粒尺寸明显细化,晶粒度由原来未微合金化钢的9.5级提高至10～10.5级;淬、回火后硬度HRC为65.2～65.8,600℃4 h红硬性HRC为62.1～62.3,Nb-RE TGM2钢制成刀具的切削寿命较原TGM2钢提高20%。展开更多
TGM2A-S钢(/%:0.85C、0.27Si、0.24Mn、0.026P、0.007S、3.98Cr、4.76Mo、6.09W、1.83V、0.12Nb、0.03RE)是在高速钢TGM2A的基础上添加微量铌和稀土开发的新型丝锥用高速钢。TGM2A-S钢的生产工艺流程为25 t EAF-30 t LF-VD(微合金化)-铸...TGM2A-S钢(/%:0.85C、0.27Si、0.24Mn、0.026P、0.007S、3.98Cr、4.76Mo、6.09W、1.83V、0.12Nb、0.03RE)是在高速钢TGM2A的基础上添加微量铌和稀土开发的新型丝锥用高速钢。TGM2A-S钢的生产工艺流程为25 t EAF-30 t LF-VD(微合金化)-铸锭(700 kg)二火锻造(85 mm方)-连轧(Φ8 mm)-冷拉(Φ6.6 mm)-加工丝锥(M6)。结果表明,原工艺:3 t中频感应炉-ESR(280 kg锭)-二火锻造(85 mm方)-连轧(Φ8 mm)-冷拉(Φ6.6 mm)-加工丝锥(M6)生产的TGM2A钢中的O和N含量分别为35.4×10^(-6)和123.6×10^(-6),而改进工艺生产的TGM2A-S钢的O和N含量分别为15.7×10^(-6)和87.7×10^(-6)。TGM2A-S钢的丝锥切削寿命较电渣工艺生产的TGM2A钢提高20%;TGM2A-S钢的淬火晶粒为10.5级,电渣工艺生产的TGM2A钢的晶粒度为10级。展开更多
基金Supported by National Nature Science Foundation of China,No.82100195China Postdoctoral Science Foundation,No.2021M700777Medical Research Project of Foshan Municipal Health Bureau,No.20230349.
文摘BACKGROUND Colon cancer is acknowledged as one of the most common malignancies worldwide,ranking third in United States regarding incidence and mortality.Notably,approximately 40%of colon cancer cases harbor oncogenic KRAS mutations,resulting in the continuous activation of epidermal growth factor receptor signaling.AIM To investigate the key pathogenic genes in KRAS mutant colon cancer holds considerable importance.METHODS Weighted gene co-expression network analysis,in combination with additional bioinformatics analysis,were conducted to screen the key factors driving the progression of KRAS mutant colon cancer.Meanwhile,various in vitro experiments were also conducted to explore the biological function of transglutaminase 2(TGM2).RESULTS Integrated analysis demonstrated that TGM2 acted as an independent prognostic factor for progression-free survival.Immunohistochemical analysis on tissue microarrays revealed that TGM2 was associated with an elevated probability of perineural invasion in patients with KRAS mutant colon cancer.Additionally,biological roles of the key gene TGM2 was also assessed,suggesting that the downregulation of TGM2 attenuated the proliferation,invasion,and migration of the KRAS mutant colon cancer cell line.CONCLUSION This study underscores the potential significance of TGM2 in the progression of KRAS mutant colon cancer.This insight not only offers a theoretical foundation for therapeutic approaches but also highlights the need for additional clinical trials and fundamental research to support our preliminary findings.
基金Supported by the Ningxia Natural Science Foundation,No.2022AAC03144.
文摘BACKGROUND Gastric cancer(GC)is a common gastrointestinal malignancy worldwide.Based on cancer-related mortality,the current prevention and treatment strategies for GC still show poor clinical results.Therefore,it is important to find effective drug treatment targets.AIM To explore the molecular mechanism of 18β-glycyrrhetinic acid(18β-GRA)regulating the miR-345-5p/TGM2 signaling pathway to inhibit the proliferation of GC cells.METHODS CCK-8 assay was used to determine the effect of 18β-GRA on the survival rate of GES-1 cells and AGS and HGC-27 cells.Cell cycle and apoptosis were detected by flow cytometry,cell migration was detected by a wound healing assay,the effect of 18β-GRA on subcutaneous tumor growth in BALB/c nude mice was investigated,and the cell autophagy level was determined by MDC staining.TMT proteomic analysis was used to detect the differentially expressed autophagy-related proteins in GC cells after 18β-GRA intervention,and then the protein-protein interaction was predicted using STRING(https://string-db.org/).MicroRNAs(miRNAs)transcriptome analysis was used to detect the miRNA differential expression profile,and use miRBase(https://www.mirbase/)and TargetScan(https://www.targetscan.org/)to predict the miRNA and complementary binding sites.Quantitative real-time polymerase chain reaction was used to detect the expression level of miRNA in 18β-GRA treated cells,and western blot was used to detect the expression of autophagy related proteins.Finally,the effect of miR-345-5p on GC cells was verified by mir-345-5p overexpression.RESULTS 18β-GRA could inhibit GC cells viability,promote cell apoptosis,block cell cycle,reduce cell wound healing ability,and inhibit the GC cells growth in vivo.MDC staining results showed that 18β-GRA could promote autophagy in GC cells.By TMT proteomic analysis and miRNAs transcriptome analysis,it was concluded that 18β-GRA could down-regulate TGM2 expression and up-regulate miR-345-5p expression in GC cells.Subsequently,we verified that TGM2 is the target of miR-345-5p,and that overexpression of miR-345-5p significantly inhibited the protein expression level of TGM2.Western blot showed that the expression of autophagy-related proteins of TGM2 and p62 was significantly reduced,and LC3II,ULK1 and AMPK expression was significantly increased in GC cells treated with 18β-GRA.Overexpression of miR-345-5p not only inhibited the expression of TGM2,but also inhibited the proliferation of GC cells by promoting cell apoptosis and arresting cell cycle.CONCLUSION 18β-GRA inhibits the proliferation of GC cells and promotes autophagy by regulating the miR-345-5p/TGM2 signaling pathway.
文摘Nb-RE微合金化TGM2高速钢(%:0.88～0.89C、4.14～4.16Cr、4.73～4.76Mo、6.09～6.12W、1.85～1.86V、0.05～0.10Nb、0.05～0.06RE)由25 t EAF-30 t LF(VD,加Nb-RE)-1 t ESR工艺冶炼。试验结果表明,经Nb-RE微合金化后,TGM2高速钢Φ96 mm材淬火晶粒尺寸明显细化,晶粒度由原来未微合金化钢的9.5级提高至10～10.5级;淬、回火后硬度HRC为65.2～65.8,600℃4 h红硬性HRC为62.1～62.3,Nb-RE TGM2钢制成刀具的切削寿命较原TGM2钢提高20%。
