Colorectal cancer(CRC)ranks among the top five most common malignant tumors worldwide and has a high mortality rate.Angiogenesis plays an important role in CRC progression;however,anti-angiogenesis therapy still has m...Colorectal cancer(CRC)ranks among the top five most common malignant tumors worldwide and has a high mortality rate.Angiogenesis plays an important role in CRC progression;however,anti-angiogenesis therapy still has many limitations.Long non-coding RNAs(lncRNAs)participate in tumor progression by regulating the expression of vascular endothelial growth factor in metastatic CRC.Thus,targeting specific lncRNAs may provide some new hope for anti-angiogenic strategies.Through analyzing data from both clinical samples and The Cancer Genome Atlas database,we found that the lncRNA LINC01503 was specifically upregulated in CRC tissues and was associated with tumor progression and poor overall survival.We also demonstrated that LINC01503 enhanced the capacity for tube formation and migration of vascular endothelial cells,thus promoting CRC tumorigenesis by upregulating vascular endothelial growth factor A(VEGFA)expression in CRC cells.Mechanistically,LINC01503 promoted the expression of VEGFA by simultaneously regulating both mRNA and protein stability of VEGFA by binding to miR-342-3p and the chaperone HSP60,respectively.The upregulation of LINC01503 in CRC cells was attributed to the CREB-binding protein CBP/p300-mediated H3K27 acetylation of the LINC01503 promoter region.Taken together,our findings clarify the mechanism by which LINC01503 may promote CRC angiogenesis,implying that LINC01503 may serve as a potential prognostic biomarker and therapeutic target for CRC.展开更多
目的探讨血府逐瘀胶囊联合顺铂对小鼠Lewis肺癌移植瘤血管新生及血管内皮生长因子A(VEGFA)、血管内皮细胞生长因子受体2(VEGFR2)表达的影响。方法从75只C57BL/6小鼠中随机取15只作为正常组,其余小鼠均进行Lewis肺癌荷瘤造模。将造模成功...目的探讨血府逐瘀胶囊联合顺铂对小鼠Lewis肺癌移植瘤血管新生及血管内皮生长因子A(VEGFA)、血管内皮细胞生长因子受体2(VEGFR2)表达的影响。方法从75只C57BL/6小鼠中随机取15只作为正常组,其余小鼠均进行Lewis肺癌荷瘤造模。将造模成功的60只小鼠随机分为模型组、顺铂组、血府逐瘀胶囊组、血府逐瘀胶囊联合顺铂组,每组15只。血府逐瘀胶囊组给予血府逐瘀胶囊0.36 g/kg灌胃,模型组给予生理盐水灌胃,均2次/d;顺铂组给予2 mg/kg的顺铂腹腔注射,2 d 1次;血府逐瘀胶囊联合顺铂组给予0.36 g/kg血府逐瘀胶囊灌胃(2次/d)和2 mg/kg的顺铂腹腔注射(2 d 1次);正常组不给予任何干预。各组连续干预15 d后,统计存活率,摘取瘤组织并称量瘤重,计算抑瘤率,免疫组化法检测肿瘤组织中微血管数量,ELISA法测定血浆VEGFA、碱性成纤维细胞生长因子(bFGF)水平,免疫印迹法检测肿瘤组织中VEGFA、VEGFR2蛋白表达情况。结果顺铂组和血府逐瘀胶囊联合顺铂组小鼠存活率明显高于模型组和血府逐瘀胶囊组(P均<0.05);血府逐瘀胶囊联合顺铂组瘤重明显低于其他组(P均<0.05),抑瘤率明显高于顺铂组和血府逐瘀胶囊组(P均<0.05),肿瘤组织中微血管数明显少于模型组和血府逐瘀胶囊组(P均<0.05);顺铂组瘤重明显低于模型组和血府逐瘀胶囊组(P均<0.05),抑瘤率明显高于血府逐瘀胶囊组(P<0.05),肿瘤组织中微血管数明显少于其他组(P均<0.05)。顺铂组血浆VEGFA、bFGF水平和肿瘤组织中VEGFA、VEGFR2蛋白相对表达量均明显低于模型组(P均<0.05);血府逐瘀胶囊联合顺铂组血浆bFGF水平和肿瘤组织中VEGFR2蛋白相对表达量均明显低于模型组(P均<0.05)。结论血府逐瘀胶囊联合顺铂对Lewis肺癌荷瘤小鼠具有显著的抑瘤及抑制肿瘤血管新生的作用,其机制可能与VEGFA/VEGFR2信号通路相关。展开更多
目的探讨造血细胞特异蛋白1相关蛋白X1(hematopoietic cell specific protein 1-associated protein X1,HAX1)和血管内皮生长因子A(vascular endothelial growth factor A,VEGFA)在脑胶质瘤中的表达及相关性,以及与患者术后生存时间、...目的探讨造血细胞特异蛋白1相关蛋白X1(hematopoietic cell specific protein 1-associated protein X1,HAX1)和血管内皮生长因子A(vascular endothelial growth factor A,VEGFA)在脑胶质瘤中的表达及相关性,以及与患者术后生存时间、预后的关系。方法UALCAN数据库分析多形性胶质母细胞瘤(glioblastoma multiforme,GBM)组织中HAX1及VEGFA mRNA的表达水平;GEPIA数据库分析GBM组织中HAX1与VEGFA表达的相关性;qRT-PCR法检测30例脑胶质瘤及12例正常脑组织中HAX1及VEGFA mRNA的表达;组织芯片结合免疫组化法检测214例脑胶质瘤组织及86例正常脑组织中HAX1和VEGFA蛋白表达水平,分析两种蛋白表达的相关性及两者与脑胶质瘤临床病理特征及患者预后的关系;GEPIA数据库进一步分析两者表达与胶质瘤患者预后的相关性。结果数据库分析结果显示,HAX1和VEGFA mRNA在GBM组织中均高表达(P=3.874100E-02,P=1.62436730732907E-12),且两者在脑胶质瘤中表达呈正相关(r=0.14,P=0.00039);qRT-PCR结果显示,HAX1(1.66±0.40)和VEGFA(2.75±0.73)mRNA在脑胶质瘤组织中均高表达(t=4.744,P<0.0001;t=8.263,P<0.0001);免疫组化结果显示,与正常脑组织相比,HAX1(67.8%,145/214)和VEGFA(72.0%,154/214)蛋白在脑胶质瘤组织中的阳性率更高(χ^(2)=29.174,P<0.05;χ^(2)=33.477,P<0.05),且两者表达呈正相关(r=0.593,P<0.05);HAX1和VEGFA蛋白表达均与行为状态评分(karnofsky performance status,KPS)、组织分化程度、WHO分级、p53及Ki-67蛋白表达密切相关(P<0.05);生存分析显示,HAX1阳性及VEGFA阳性患者的总生存率(5.5%、6.5%)明显低于HAX1阴性患者(62.3%、68.3%)(P<0.001),且两者均阳性的患者总生存率(4.6%)更低(P<0.001);预后分析显示,HAX1蛋白阳性(HR=1.746,P=0.026)、VEGFA蛋白阳性(HR=2.760,P<0.001)、组织中+低分化(HR=3.097,P=0.034)、WHO高分级(HR=1.533,P=0.005)及Ki-67蛋白阳性(HR=1.827,P=0.011)是患者预后的独立危险因素。GEPIA数据库分析结果亦显示,HAX1(HR=1.4,P=0.004)与VEGFA(HR=4.2,P<0.01)表达与患者生存呈负相关。结论HAX1和VEGFA在脑胶质瘤中高表达,其参与了脑胶质瘤的恶性生物学进展,并影响患者预后。展开更多
基金supported by the National Natural Science Foundation of China(Grant No.81972288)the Scientific and Technologic Development Programme of Suzhou(Livelihood Science and Technology-Applied Basic Research in Healthcare,SYS2020057).
文摘Colorectal cancer(CRC)ranks among the top five most common malignant tumors worldwide and has a high mortality rate.Angiogenesis plays an important role in CRC progression;however,anti-angiogenesis therapy still has many limitations.Long non-coding RNAs(lncRNAs)participate in tumor progression by regulating the expression of vascular endothelial growth factor in metastatic CRC.Thus,targeting specific lncRNAs may provide some new hope for anti-angiogenic strategies.Through analyzing data from both clinical samples and The Cancer Genome Atlas database,we found that the lncRNA LINC01503 was specifically upregulated in CRC tissues and was associated with tumor progression and poor overall survival.We also demonstrated that LINC01503 enhanced the capacity for tube formation and migration of vascular endothelial cells,thus promoting CRC tumorigenesis by upregulating vascular endothelial growth factor A(VEGFA)expression in CRC cells.Mechanistically,LINC01503 promoted the expression of VEGFA by simultaneously regulating both mRNA and protein stability of VEGFA by binding to miR-342-3p and the chaperone HSP60,respectively.The upregulation of LINC01503 in CRC cells was attributed to the CREB-binding protein CBP/p300-mediated H3K27 acetylation of the LINC01503 promoter region.Taken together,our findings clarify the mechanism by which LINC01503 may promote CRC angiogenesis,implying that LINC01503 may serve as a potential prognostic biomarker and therapeutic target for CRC.
文摘目的探讨血府逐瘀胶囊联合顺铂对小鼠Lewis肺癌移植瘤血管新生及血管内皮生长因子A(VEGFA)、血管内皮细胞生长因子受体2(VEGFR2)表达的影响。方法从75只C57BL/6小鼠中随机取15只作为正常组,其余小鼠均进行Lewis肺癌荷瘤造模。将造模成功的60只小鼠随机分为模型组、顺铂组、血府逐瘀胶囊组、血府逐瘀胶囊联合顺铂组,每组15只。血府逐瘀胶囊组给予血府逐瘀胶囊0.36 g/kg灌胃,模型组给予生理盐水灌胃,均2次/d;顺铂组给予2 mg/kg的顺铂腹腔注射,2 d 1次;血府逐瘀胶囊联合顺铂组给予0.36 g/kg血府逐瘀胶囊灌胃(2次/d)和2 mg/kg的顺铂腹腔注射(2 d 1次);正常组不给予任何干预。各组连续干预15 d后,统计存活率,摘取瘤组织并称量瘤重,计算抑瘤率,免疫组化法检测肿瘤组织中微血管数量,ELISA法测定血浆VEGFA、碱性成纤维细胞生长因子(bFGF)水平,免疫印迹法检测肿瘤组织中VEGFA、VEGFR2蛋白表达情况。结果顺铂组和血府逐瘀胶囊联合顺铂组小鼠存活率明显高于模型组和血府逐瘀胶囊组(P均<0.05);血府逐瘀胶囊联合顺铂组瘤重明显低于其他组(P均<0.05),抑瘤率明显高于顺铂组和血府逐瘀胶囊组(P均<0.05),肿瘤组织中微血管数明显少于模型组和血府逐瘀胶囊组(P均<0.05);顺铂组瘤重明显低于模型组和血府逐瘀胶囊组(P均<0.05),抑瘤率明显高于血府逐瘀胶囊组(P<0.05),肿瘤组织中微血管数明显少于其他组(P均<0.05)。顺铂组血浆VEGFA、bFGF水平和肿瘤组织中VEGFA、VEGFR2蛋白相对表达量均明显低于模型组(P均<0.05);血府逐瘀胶囊联合顺铂组血浆bFGF水平和肿瘤组织中VEGFR2蛋白相对表达量均明显低于模型组(P均<0.05)。结论血府逐瘀胶囊联合顺铂对Lewis肺癌荷瘤小鼠具有显著的抑瘤及抑制肿瘤血管新生的作用,其机制可能与VEGFA/VEGFR2信号通路相关。
