BACKGROUND Monopolar spindle-binding protein 3B(MOB3B)functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers.AIM To investigate the role of MOB3B in colorecta...BACKGROUND Monopolar spindle-binding protein 3B(MOB3B)functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers.AIM To investigate the role of MOB3B in colorectal cancer(CRC).METHODS This study collected 102 CRC tissue samples for immunohistochemical detection of MOB3B expression for association with CRC prognosis.After overexpression and knockdown of MOB3B expression were induced in CRC cell lines,changes in cell viability,migration,invasion,and gene expression were assayed.Tumor cell autophagy was detected using transmission electron microscopy,while nude mouse xenograft experiments were performed to confirm the in-vitro results.RESULTS MOB3B expression was reduced in CRC vs normal tissues and loss of MOB3B expression was associated with poor CRC prognosis.Overexpression of MOB3B protein in vitro attenuated the cell viability as well as the migration and invasion capacities of CRC cells,whereas knockdown of MOB3B expression had the opposite effects in CRC cells.At the molecular level,microtubule-associated protein light chain 3 II/I expression was elevated,whereas the expression of matrix metalloproteinase(MMP)2,MMP9,sequestosome 1,and phosphorylated mechanistic target of rapamycin kinase(mTOR)was downregulated in MOB3B-overexpressing RKO cells.In contrast,the opposite results were observed in tumor cells with MOB3B knockdown.The nude mouse data confirmed these in-vitro findings,i.e.,MOB3B expression suppressed CRC cell xenograft growth,whereas knockdown of MOB3B expression promoted the growth of CRC cell xenografts.CONCLUSION Loss of MOB3B expression promotes CRC development and malignant behaviors,suggesting a potential tumor suppressive role of MOB3B in CRC by inhibition of mTOR/autophagy signaling.展开更多
In this editorial,we review the work of Razali et al published in World J Gas-troenterology,with a particular focus on the effect of rs10889677 variation in the phosphatidylinositol 3-kinase(PI3K)pathway and buparlisi...In this editorial,we review the work of Razali et al published in World J Gas-troenterology,with a particular focus on the effect of rs10889677 variation in the phosphatidylinositol 3-kinase(PI3K)pathway and buparlisib on colitis-associated cancer.The role of PI3K in promoting cancer progression has been widely recognized,as it is involved in regulating the survival,differentiation,and prolif-eration of cancer cells.The complement Clq/TNF-related protein 6(CTRP6)is a newer tumor-associated factor.Recent studies have revealed the pro-tumor effect of CTRP6 in gastric cancer,hepatocellular carcinoma,colorectal cancer,and other gastrointestinal tumors through the PI3K pathway.This article attempts to reveal the mechanism through which the CTRP6 affects the development of digestive system tumors through the PI3K pathway by summarizing recent research.展开更多
Recently,the roles of pyroptosis,a form of cell death induced by activated NODlike receptor protein 3(NLRP3)inflammasome,in the pathogenesis of diabetic cardiomyopathy(DCM)have been extensively investigated.However,mo...Recently,the roles of pyroptosis,a form of cell death induced by activated NODlike receptor protein 3(NLRP3)inflammasome,in the pathogenesis of diabetic cardiomyopathy(DCM)have been extensively investigated.However,most studies have focused mainly on whether diabetes increases the NLRP3 inflammasome and associated pyroptosis in the heart of type 1 or type 2 diabetic rodent models,and whether various medications and natural products prevent the development of DCM,associated with decreased levels of cardiac NLRP3 inflammasome and pyroptosis.The direct link of NLRP3 inflammasome and associated pyroptosis to the pathogenesis of DCM remains unclear based on the limited evidence derived from the available studies,with the approaches of NLRP3 gene silencing or pharmaceutical application of NLRP3 specific inhibitors.We thus emphasize the requirement for more systematic studies that are designed to provide direct evidence to support the link,given that several studies have provided both direct and indirect evidence under specific conditions.This editorial emphasizes that the current investigation should be circumspect in its conclusion,i.e.,not overemphasizing its role in the pathogenesis of DCM with the fact of only significantly increased expression or activation of NLRP3 inflammasome and pyroptosis in the heart of diabetic rodent models.Only clear-cut evidence-based causative roles of NLRP3 inflammasome and pyroptosis in the pathogenesis of DCM can help to develop effective and safe medications for the clinical management of DCM,targeting these biomarkers.展开更多
BACKGROUND Pancreatic cancer is a highly invasive malignant tumor. Expression levels of the autophagy-related protein microtubule-associated protein 1 A/1 B-light chain 3(LC3) and perineural invasion(PNI) are closely ...BACKGROUND Pancreatic cancer is a highly invasive malignant tumor. Expression levels of the autophagy-related protein microtubule-associated protein 1 A/1 B-light chain 3(LC3) and perineural invasion(PNI) are closely related to its occurrence and development. Our previous results showed that the high expression of LC3 was positively correlated with PNI in the patients with pancreatic cancer. In this study, we further searched for differential genes involved in autophagy of pancreatic cancer by gene expression profiling and analyzed their biological functions in pancreatic cancer, which provides a theoretical basis for elucidating the pathophysiological mechanism of autophagy in pancreatic cancer and PNI.AIM To identify differentially expressed genes involved in pancreatic cancer autophagy and explore the pathogenesis at the molecular level.METHODS Two sets of gene expression profiles of pancreatic cancer/normal tissue(GSE16515 and GSE15471) were collected from the Gene Expression Omnibus.Significance analysis of microarrays algorithm was used to screen differentially expressed genes related to pancreatic cancer. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were used to analyze the functional enrichment of the differentially expressed genes. Protein interaction data containing only differentially expressed genes was downloaded from String database and screened. Module mining was carried out by Cytoscape software and ClusterOne plug-in. The interaction relationship between the modules was analyzed and the pivot nodes between the functional modules were determined according to the information of the functional modules and the data of reliable protein interaction network.RESULTS Based on the above two data sets of pancreatic tissue total gene expression, 6098 and 12928 differentially expressed genes were obtained by analysis of genes with higher phenotypic correlation. After extracting the intersection of the two differential gene sets, 4870 genes were determined. GO analysis showed that 14 significant functional items including negative regulation of protein ubiquitination were closely related to autophagy. A total of 986 differentially expressed genes were enriched in these functional items. After eliminating the autophagy related genes of human cancer cells which had been defined, 347 differentially expressed genes were obtained. KEGG pathway analysis showed that the pathways hsa04144 and hsa04020 were related to autophagy. In addition,65 clustering modules were screened after the protein interaction network was constructed based on String database, and module 32 contains the LC3 gene,which interacts with multiple autophagy-related genes. Moreover, ubiquitin C acts as a pivot node in functional modules to connect multiple modules related to pancreatic cancer and autophagy.CONCLUSION Three hundred and forty-seven genes associated with autophagy in human pancreatic cancer were concentrated, and a key gene ubiquitin C which is closely related to the occurrence of PNI was determined, suggesting that LC3 may influence the PNI and prognosis of pancreatic cancer through ubiquitin C.展开更多
目的探讨血清几丁质酶-3样蛋白1(chitinase 3-like protein 1,CHI3L1)与血液透析患者全因死亡和心脑血管疾病死亡之间的关系。方法本研究为前瞻性队列研究,病例来自2014年9月北京大学第三医院肾内科维持性血液透析患者。测定基线血CHI3L...目的探讨血清几丁质酶-3样蛋白1(chitinase 3-like protein 1,CHI3L1)与血液透析患者全因死亡和心脑血管疾病死亡之间的关系。方法本研究为前瞻性队列研究,病例来自2014年9月北京大学第三医院肾内科维持性血液透析患者。测定基线血CHI3L1水平,并根据中位数将患者分为高CHI3L1组和低CHI3L1组,随访9年。用Kaplan-Meier生存分析高CHI3L1组和低CHI3L1组患者生存率的差异,用限制性立方样条(restricted cubic spline,RCS)曲线描述CHI3L1与全因死亡率的剂量反应关系,用多因素COX比例风险模型分析患者全因死亡或心脑血管疾病死亡的独立危险因素。结果共纳入109例患者,随访时间为80.0(38.2,113.2)个月。Kaplan-Meier生存分析显示高CHI3L1组患者全因死亡率高于低CHI3L1组(χ^(2)=4.720,P=0.030),2组患者心脑血管疾病死亡率无明显差异(χ^(2)=1.954,P=0.162)。当CHI3L1≥199.8 ng/ml时,全因死亡率随着CHI3L1水平的增加有明显增加(HR=1.747,95%CI:1.035~2.947,P=0.037)。COX回归分析结果显示:年龄增加(HR=1.029,95%CI:1.001~1.056,P=0.040)、长透析龄(HR=2.251,95%CI:1.310~3.868,P=0.003)、收缩压高(HR=1.022,95%CI:1.008~1.036,P=0.002)、血肌酐低(HR=0.135,95%CI:0.064~0.283,P<0.001)均为血液透析患者全因死亡的独立危险因素,多种因素校正后高CHI3L1仍然是患者全因死亡的独立危险因素(HR=1.963,95%CI:1.010~3.813,P=0.047)。结论高CHI3L1组患者全因死亡率高于低CHI3L1组患者,血CHI3L1可能是血液透析患者全因死亡的独立预测指标。展开更多
目的研究程序性细胞死亡蛋白4(programmed cell death protein 4,PDCD4)在脓毒症诱导的急性肾损伤(acute kidney injury,AKI)中的作用机制,以及调控PDCD4表达通过丝裂原活化蛋白激酶3(mitogen-activated protein kinase 3,MAP2K3)和p38...目的研究程序性细胞死亡蛋白4(programmed cell death protein 4,PDCD4)在脓毒症诱导的急性肾损伤(acute kidney injury,AKI)中的作用机制,以及调控PDCD4表达通过丝裂原活化蛋白激酶3(mitogen-activated protein kinase 3,MAP2K3)和p38蛋白激酶(p38 mitogen-activated protein kinase,p38 MAPK)对脓毒症AKI起到潜在治疗作用。方法用脂多糖(lipopolysaccharide,LPS)刺激人肾小管上皮细胞(HK-2)构建脓毒症AKI细胞模型。进一步用腺病毒介导siRNA和过表达载体抑制和上调AKI细胞模型中PDCD4的表达;CCK-8法检测细胞增殖;用DCFH-DA及激光共聚焦显微镜检测细胞中ROS水平,用总SOD活性检测试剂和MDA检测试剂盒检测细胞中SOD和MDA水平;免疫共沉淀验证PDCD4和MAP2K3之间的蛋白相互作用;TUNEL染色法检测细胞凋亡;RT-qPCR和Western blot检测PDCD4及相关基因的mRNA和蛋白表达水平;ELISA法检测患者血清中炎症相关因子水平。结果LPS诱导可以促进HK-2细胞中PDCD4表达,下调PDCD4可抑制LPS诱导的HK-2细胞的炎症、氧化应激及细胞凋亡。数据库预测及免疫共沉淀证实PDCD4可以与MAP2K3相互作用,且在LPS诱导的HK-2细胞中,MAP2K3表达水平显著增强。MAP2K3过表达和p38 MAPK激动剂可以减轻PDCD4下调对LPS诱导的细胞炎症和氧化应激的影响并抑制细胞凋亡。结论下调PDCD4可以通过抑制MAP2K3和p38 MAPK从而抑制LPS诱导的肾小管上皮细胞的炎症和凋亡。展开更多
基金Supported by National Natural Science Foundation of China,No.81760516Natural Science Foundation of Guangxi,China,No.2019GXNSFAA185030+1 种基金Self-Financed Scientific Research Projects of Guangxi Zhuang Autonomous Region Health and Family Planning Commission,China,No.Z20181003Guangxi Medical University Youth Science Fund Project,China,No.GXMUYSF202221.
文摘BACKGROUND Monopolar spindle-binding protein 3B(MOB3B)functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers.AIM To investigate the role of MOB3B in colorectal cancer(CRC).METHODS This study collected 102 CRC tissue samples for immunohistochemical detection of MOB3B expression for association with CRC prognosis.After overexpression and knockdown of MOB3B expression were induced in CRC cell lines,changes in cell viability,migration,invasion,and gene expression were assayed.Tumor cell autophagy was detected using transmission electron microscopy,while nude mouse xenograft experiments were performed to confirm the in-vitro results.RESULTS MOB3B expression was reduced in CRC vs normal tissues and loss of MOB3B expression was associated with poor CRC prognosis.Overexpression of MOB3B protein in vitro attenuated the cell viability as well as the migration and invasion capacities of CRC cells,whereas knockdown of MOB3B expression had the opposite effects in CRC cells.At the molecular level,microtubule-associated protein light chain 3 II/I expression was elevated,whereas the expression of matrix metalloproteinase(MMP)2,MMP9,sequestosome 1,and phosphorylated mechanistic target of rapamycin kinase(mTOR)was downregulated in MOB3B-overexpressing RKO cells.In contrast,the opposite results were observed in tumor cells with MOB3B knockdown.The nude mouse data confirmed these in-vitro findings,i.e.,MOB3B expression suppressed CRC cell xenograft growth,whereas knockdown of MOB3B expression promoted the growth of CRC cell xenografts.CONCLUSION Loss of MOB3B expression promotes CRC development and malignant behaviors,suggesting a potential tumor suppressive role of MOB3B in CRC by inhibition of mTOR/autophagy signaling.
文摘In this editorial,we review the work of Razali et al published in World J Gas-troenterology,with a particular focus on the effect of rs10889677 variation in the phosphatidylinositol 3-kinase(PI3K)pathway and buparlisib on colitis-associated cancer.The role of PI3K in promoting cancer progression has been widely recognized,as it is involved in regulating the survival,differentiation,and prolif-eration of cancer cells.The complement Clq/TNF-related protein 6(CTRP6)is a newer tumor-associated factor.Recent studies have revealed the pro-tumor effect of CTRP6 in gastric cancer,hepatocellular carcinoma,colorectal cancer,and other gastrointestinal tumors through the PI3K pathway.This article attempts to reveal the mechanism through which the CTRP6 affects the development of digestive system tumors through the PI3K pathway by summarizing recent research.
文摘Recently,the roles of pyroptosis,a form of cell death induced by activated NODlike receptor protein 3(NLRP3)inflammasome,in the pathogenesis of diabetic cardiomyopathy(DCM)have been extensively investigated.However,most studies have focused mainly on whether diabetes increases the NLRP3 inflammasome and associated pyroptosis in the heart of type 1 or type 2 diabetic rodent models,and whether various medications and natural products prevent the development of DCM,associated with decreased levels of cardiac NLRP3 inflammasome and pyroptosis.The direct link of NLRP3 inflammasome and associated pyroptosis to the pathogenesis of DCM remains unclear based on the limited evidence derived from the available studies,with the approaches of NLRP3 gene silencing or pharmaceutical application of NLRP3 specific inhibitors.We thus emphasize the requirement for more systematic studies that are designed to provide direct evidence to support the link,given that several studies have provided both direct and indirect evidence under specific conditions.This editorial emphasizes that the current investigation should be circumspect in its conclusion,i.e.,not overemphasizing its role in the pathogenesis of DCM with the fact of only significantly increased expression or activation of NLRP3 inflammasome and pyroptosis in the heart of diabetic rodent models.Only clear-cut evidence-based causative roles of NLRP3 inflammasome and pyroptosis in the pathogenesis of DCM can help to develop effective and safe medications for the clinical management of DCM,targeting these biomarkers.
基金Supported by the National Natural Science Foundation of China,No.U1504815 and No.U1504808
文摘BACKGROUND Pancreatic cancer is a highly invasive malignant tumor. Expression levels of the autophagy-related protein microtubule-associated protein 1 A/1 B-light chain 3(LC3) and perineural invasion(PNI) are closely related to its occurrence and development. Our previous results showed that the high expression of LC3 was positively correlated with PNI in the patients with pancreatic cancer. In this study, we further searched for differential genes involved in autophagy of pancreatic cancer by gene expression profiling and analyzed their biological functions in pancreatic cancer, which provides a theoretical basis for elucidating the pathophysiological mechanism of autophagy in pancreatic cancer and PNI.AIM To identify differentially expressed genes involved in pancreatic cancer autophagy and explore the pathogenesis at the molecular level.METHODS Two sets of gene expression profiles of pancreatic cancer/normal tissue(GSE16515 and GSE15471) were collected from the Gene Expression Omnibus.Significance analysis of microarrays algorithm was used to screen differentially expressed genes related to pancreatic cancer. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were used to analyze the functional enrichment of the differentially expressed genes. Protein interaction data containing only differentially expressed genes was downloaded from String database and screened. Module mining was carried out by Cytoscape software and ClusterOne plug-in. The interaction relationship between the modules was analyzed and the pivot nodes between the functional modules were determined according to the information of the functional modules and the data of reliable protein interaction network.RESULTS Based on the above two data sets of pancreatic tissue total gene expression, 6098 and 12928 differentially expressed genes were obtained by analysis of genes with higher phenotypic correlation. After extracting the intersection of the two differential gene sets, 4870 genes were determined. GO analysis showed that 14 significant functional items including negative regulation of protein ubiquitination were closely related to autophagy. A total of 986 differentially expressed genes were enriched in these functional items. After eliminating the autophagy related genes of human cancer cells which had been defined, 347 differentially expressed genes were obtained. KEGG pathway analysis showed that the pathways hsa04144 and hsa04020 were related to autophagy. In addition,65 clustering modules were screened after the protein interaction network was constructed based on String database, and module 32 contains the LC3 gene,which interacts with multiple autophagy-related genes. Moreover, ubiquitin C acts as a pivot node in functional modules to connect multiple modules related to pancreatic cancer and autophagy.CONCLUSION Three hundred and forty-seven genes associated with autophagy in human pancreatic cancer were concentrated, and a key gene ubiquitin C which is closely related to the occurrence of PNI was determined, suggesting that LC3 may influence the PNI and prognosis of pancreatic cancer through ubiquitin C.
文摘目的研究程序性细胞死亡蛋白4(programmed cell death protein 4,PDCD4)在脓毒症诱导的急性肾损伤(acute kidney injury,AKI)中的作用机制,以及调控PDCD4表达通过丝裂原活化蛋白激酶3(mitogen-activated protein kinase 3,MAP2K3)和p38蛋白激酶(p38 mitogen-activated protein kinase,p38 MAPK)对脓毒症AKI起到潜在治疗作用。方法用脂多糖(lipopolysaccharide,LPS)刺激人肾小管上皮细胞(HK-2)构建脓毒症AKI细胞模型。进一步用腺病毒介导siRNA和过表达载体抑制和上调AKI细胞模型中PDCD4的表达;CCK-8法检测细胞增殖;用DCFH-DA及激光共聚焦显微镜检测细胞中ROS水平,用总SOD活性检测试剂和MDA检测试剂盒检测细胞中SOD和MDA水平;免疫共沉淀验证PDCD4和MAP2K3之间的蛋白相互作用;TUNEL染色法检测细胞凋亡;RT-qPCR和Western blot检测PDCD4及相关基因的mRNA和蛋白表达水平;ELISA法检测患者血清中炎症相关因子水平。结果LPS诱导可以促进HK-2细胞中PDCD4表达,下调PDCD4可抑制LPS诱导的HK-2细胞的炎症、氧化应激及细胞凋亡。数据库预测及免疫共沉淀证实PDCD4可以与MAP2K3相互作用,且在LPS诱导的HK-2细胞中,MAP2K3表达水平显著增强。MAP2K3过表达和p38 MAPK激动剂可以减轻PDCD4下调对LPS诱导的细胞炎症和氧化应激的影响并抑制细胞凋亡。结论下调PDCD4可以通过抑制MAP2K3和p38 MAPK从而抑制LPS诱导的肾小管上皮细胞的炎症和凋亡。
