BACKGROUND Colon cancer represents a significant malignant neoplasm within the digestive system,characterized by a high incidence rate and substantial disease burden.The F-box protein 22(FBXO22)plays a role in forming...BACKGROUND Colon cancer represents a significant malignant neoplasm within the digestive system,characterized by a high incidence rate and substantial disease burden.The F-box protein 22(FBXO22)plays a role in forming a specific type of ubiquitin ligase subunit,which is expressed abnormally in various malignant neoplasms and shows a notable relationship with prognosis in patients with cancer.Never-theless,the function of FBXO22 in the context of colon cancer remains inade-quately elucidated.AIM To explore the role of FBXO22 in colon cancer by examining FBXO22 expression patterns and analyzing how the protein affects the prognosis in patients who have undergone surgery.METHODS Samples of cancerous and nearby normal tissues from patients with colon cancer were gathered,along with pertinent clinical data.Expression levels of the FBXO22 gene in both cancerous and paracancerous tissues were assessed through immu-nohistochemistry.The median H score served as a criterion for categorizing FBXO22 gene expression into high and low levels in cancerous tissues,and the relationship between these expression levels and various pathologic character-istics of patients,such as age,sex,and clinical stage,was analyzed.Colon cancer cell lines HCT116 and DLD-1 were used and divided into three groups:A blank control group,a negative control group,and a si-FBXO22 group.FBXO22 gene mRNA and protein expression were measured 24 hours post-transfection using real-time fluorescence quantitative polymerase chain reaction and western blotting.The proliferation capabilities of the cells in each group were assessed using the Cell Counting Kit-8 assay and 5-ethynyl-2’-deoxyuridine assay,while cellular migration and invasion abilities were evaluated using scratch healing and Transwell assays.Various online platforms,including the Timer Immune Estimation Resource,were used to analyze pan-cancer expression,promoter methylation levels,and mutation frequencies of the FBXO22 gene in colon cancer patients.Additionally,the correlation between FBXO22 gene expression,patient prognosis,immune cell infiltration,and the expression of immune molecules in the colon cancer microenvironment was investigated.The relationship between FBXO22 gene expression and chemotherapy resistance,along with the potential mechanisms of action of the FBXO22 gene,were analyzed using The Cancer Genome Atlas dataset and the Genomics of Drug Sensitivity in Cancer drug training set via R software.RESULTS Compared with normal colonic tissues,the FBXO22 gene was highly expressed in colon cancer tissues.Post-operative patients with colon cancer elevated FBXO22 reduced survival and exhibited resistance to various chemotherapeutic agents.FBXO22 expression suppresses the infiltration of anti-tumor immune cells.In vitro,FBXO22 knockdown inhibited the proliferation and migration of colon cancer cells.CONCLUSION The FBXO22 gene is a biomarker of poor prognosis in patients with colon cancer and has potential as a target for immunotherapy and overcoming chemotherapy resistance.展开更多
BACKGROUND The mortality rate for severe cases of acute pancreatitis(AP),a common gastrointestinal emergency,is as high as 30%.Our previous study has shown that rutaecarpine(Rut)has a therapeutic effect on AP.AIM To i...BACKGROUND The mortality rate for severe cases of acute pancreatitis(AP),a common gastrointestinal emergency,is as high as 30%.Our previous study has shown that rutaecarpine(Rut)has a therapeutic effect on AP.AIM To investigate the role of F-box and WD repeat domain containing 11(FBXW11)in AP models and to assess whether Rut mitigates AP by regulating FBXW11.METHODS AP rat model was established and treated with Rut,followed by biochemical analysis of serum amylase and lipase,hematoxylin and eosin staining of pancreatic tissue,and immunohistochemistry detection of pancreatic Ly6G,CD11b,and myeloperoxidase.Assay kits were used to detect oxidative stress-related indicators in pancreatic tissue and inflammatory factors in serum.AR42J cells were treated with cerulein to model AP and subjected to Cell Counting Kit-8 viability assay,flow cytometry apoptosis assay,and immunofluorescence detection of reactive oxygen species to elucidate the mechanistic involvement of the enhancer of zeste homolog 2(EZH2)-FBXW11 axis in Rut-mediated protection against AP.The EZH2-histone H3 binding and H3 methylation were evaluated using co-immunoprecipitation.RESULTS Rut treatment ameliorated AP severity,as evidenced by reduced serum levels of pancreatic enzymes(amylase and lipase)and attenuated histological damage.Rut also decreased inflammatory markers(interleukin-1 beta,interleukin-6,and tumor necrosis factor alpha),tissue oxidative stress(malondialdehyde),and neutrophil infiltration(Ly6G,CD11b,and myeloperoxidase)levels in rats with AP.Moreover,Rut restored pancreatic antioxidant capacity(glutathione and superoxide dismutase).In vitro,Rut pre-incubation enhanced cell viability and suppressed cerulein-induced apoptosis and oxidative stress.Rut increased EZH2 expression while decreasing FBXW11 expression.FBXW11 overexpression eliminated the protective effect of Rut against AP.Further analysis revealed that EZH2 binds to H3 and upregulates H3 methylation levels,thereby inhibiting FBXW11 expression.CONCLUSION Collectively,our findings demonstrate that Rut ameliorates AP by upregulating EZH2,thereby enhancing H3 methylation and suppressing FBXW11 expression.展开更多
F-box蛋白作为SCF(Skp1,Cullin and an F-box protein)复合体的成员,参与调节植物的生长发育过程。At5g22700为功能未知的F-box基因家族成员。本研究通过酵母双杂交分析At5g22700蛋白与ASK(Arabidopsis-SKP1-like)家族蛋白的相互作用,发...F-box蛋白作为SCF(Skp1,Cullin and an F-box protein)复合体的成员,参与调节植物的生长发育过程。At5g22700为功能未知的F-box基因家族成员。本研究通过酵母双杂交分析At5g22700蛋白与ASK(Arabidopsis-SKP1-like)家族蛋白的相互作用,发现At5g22700蛋白的F-box结构域与ASK4蛋白相互作用。实时定量PCR分析该基因在不同组织器官中的表达,发现该基因在根和花中的表达量最高,说明At5g22700可能在根和花的发育中具有重要作用。以At5g22700基因的T-DNA插入突变体和过量表达转基因株系为材料,分析不同光照条件下幼苗的表型,发现蓝光下At5g22700过量表达转基因幼苗的主根比野生型长。这些研究结果表明,At5g22700在植物体内可能形成SCF复合体,并在植物幼苗主根伸长生长中起促进作用。展开更多
基金The study was reviewed and approved by institutional ethics board of Affiliated Hospital of Hebei Engineering University(No.:2024[K]005-01).
文摘BACKGROUND Colon cancer represents a significant malignant neoplasm within the digestive system,characterized by a high incidence rate and substantial disease burden.The F-box protein 22(FBXO22)plays a role in forming a specific type of ubiquitin ligase subunit,which is expressed abnormally in various malignant neoplasms and shows a notable relationship with prognosis in patients with cancer.Never-theless,the function of FBXO22 in the context of colon cancer remains inade-quately elucidated.AIM To explore the role of FBXO22 in colon cancer by examining FBXO22 expression patterns and analyzing how the protein affects the prognosis in patients who have undergone surgery.METHODS Samples of cancerous and nearby normal tissues from patients with colon cancer were gathered,along with pertinent clinical data.Expression levels of the FBXO22 gene in both cancerous and paracancerous tissues were assessed through immu-nohistochemistry.The median H score served as a criterion for categorizing FBXO22 gene expression into high and low levels in cancerous tissues,and the relationship between these expression levels and various pathologic character-istics of patients,such as age,sex,and clinical stage,was analyzed.Colon cancer cell lines HCT116 and DLD-1 were used and divided into three groups:A blank control group,a negative control group,and a si-FBXO22 group.FBXO22 gene mRNA and protein expression were measured 24 hours post-transfection using real-time fluorescence quantitative polymerase chain reaction and western blotting.The proliferation capabilities of the cells in each group were assessed using the Cell Counting Kit-8 assay and 5-ethynyl-2’-deoxyuridine assay,while cellular migration and invasion abilities were evaluated using scratch healing and Transwell assays.Various online platforms,including the Timer Immune Estimation Resource,were used to analyze pan-cancer expression,promoter methylation levels,and mutation frequencies of the FBXO22 gene in colon cancer patients.Additionally,the correlation between FBXO22 gene expression,patient prognosis,immune cell infiltration,and the expression of immune molecules in the colon cancer microenvironment was investigated.The relationship between FBXO22 gene expression and chemotherapy resistance,along with the potential mechanisms of action of the FBXO22 gene,were analyzed using The Cancer Genome Atlas dataset and the Genomics of Drug Sensitivity in Cancer drug training set via R software.RESULTS Compared with normal colonic tissues,the FBXO22 gene was highly expressed in colon cancer tissues.Post-operative patients with colon cancer elevated FBXO22 reduced survival and exhibited resistance to various chemotherapeutic agents.FBXO22 expression suppresses the infiltration of anti-tumor immune cells.In vitro,FBXO22 knockdown inhibited the proliferation and migration of colon cancer cells.CONCLUSION The FBXO22 gene is a biomarker of poor prognosis in patients with colon cancer and has potential as a target for immunotherapy and overcoming chemotherapy resistance.
基金Supported by Hunan Provincial Natural Science Foundation of China,No.2022JJ40836the Key Project of Research and Development Plan of Hunan Province,No.2023DK2002the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation,No.GZC20242045.
文摘BACKGROUND The mortality rate for severe cases of acute pancreatitis(AP),a common gastrointestinal emergency,is as high as 30%.Our previous study has shown that rutaecarpine(Rut)has a therapeutic effect on AP.AIM To investigate the role of F-box and WD repeat domain containing 11(FBXW11)in AP models and to assess whether Rut mitigates AP by regulating FBXW11.METHODS AP rat model was established and treated with Rut,followed by biochemical analysis of serum amylase and lipase,hematoxylin and eosin staining of pancreatic tissue,and immunohistochemistry detection of pancreatic Ly6G,CD11b,and myeloperoxidase.Assay kits were used to detect oxidative stress-related indicators in pancreatic tissue and inflammatory factors in serum.AR42J cells were treated with cerulein to model AP and subjected to Cell Counting Kit-8 viability assay,flow cytometry apoptosis assay,and immunofluorescence detection of reactive oxygen species to elucidate the mechanistic involvement of the enhancer of zeste homolog 2(EZH2)-FBXW11 axis in Rut-mediated protection against AP.The EZH2-histone H3 binding and H3 methylation were evaluated using co-immunoprecipitation.RESULTS Rut treatment ameliorated AP severity,as evidenced by reduced serum levels of pancreatic enzymes(amylase and lipase)and attenuated histological damage.Rut also decreased inflammatory markers(interleukin-1 beta,interleukin-6,and tumor necrosis factor alpha),tissue oxidative stress(malondialdehyde),and neutrophil infiltration(Ly6G,CD11b,and myeloperoxidase)levels in rats with AP.Moreover,Rut restored pancreatic antioxidant capacity(glutathione and superoxide dismutase).In vitro,Rut pre-incubation enhanced cell viability and suppressed cerulein-induced apoptosis and oxidative stress.Rut increased EZH2 expression while decreasing FBXW11 expression.FBXW11 overexpression eliminated the protective effect of Rut against AP.Further analysis revealed that EZH2 binds to H3 and upregulates H3 methylation levels,thereby inhibiting FBXW11 expression.CONCLUSION Collectively,our findings demonstrate that Rut ameliorates AP by upregulating EZH2,thereby enhancing H3 methylation and suppressing FBXW11 expression.
文摘F-box蛋白作为SCF(Skp1,Cullin and an F-box protein)复合体的成员,参与调节植物的生长发育过程。At5g22700为功能未知的F-box基因家族成员。本研究通过酵母双杂交分析At5g22700蛋白与ASK(Arabidopsis-SKP1-like)家族蛋白的相互作用,发现At5g22700蛋白的F-box结构域与ASK4蛋白相互作用。实时定量PCR分析该基因在不同组织器官中的表达,发现该基因在根和花中的表达量最高,说明At5g22700可能在根和花的发育中具有重要作用。以At5g22700基因的T-DNA插入突变体和过量表达转基因株系为材料,分析不同光照条件下幼苗的表型,发现蓝光下At5g22700过量表达转基因幼苗的主根比野生型长。这些研究结果表明,At5g22700在植物体内可能形成SCF复合体,并在植物幼苗主根伸长生长中起促进作用。
