Backgrounds and Objective Angiopoietin-2(Ang-2)is a promising biomarker and therapeutic target for gastrointestinal angiodysplasia(GIAD).We hypothesized that the lncRNA-HIF1A-AS2/miR-153-3p/HIF-1α/Ang-2 axis plays a ...Backgrounds and Objective Angiopoietin-2(Ang-2)is a promising biomarker and therapeutic target for gastrointestinal angiodysplasia(GIAD).We hypothesized that the lncRNA-HIF1A-AS2/miR-153-3p/HIF-1α/Ang-2 axis plays a critical role in small bowel angiodysplasia(SBAD)-associated angiogenesis,which can be blocked by rifaximin.The purpose of this study was to investigate the expression and pro-angiogenic effects of the lncRNA-HIF1A-AS2/miR-153-3p/HIF-1α/Ang-2 in SBAD and to evaluate the therapeutic potential of rifaximin on SBAD by targeting this axis.Methods The expression and pro-angiogenic effects of lncRNA-HIF1A-AS2/miR-153-3p/HIF-1α/Ang-2 were analysed in SBAD tissues and human umbilical vein endothelial cells(HUVECs).The anti-angiogenic effect of rifaximin and its impact on the lncRNA-HIF1A-AS2/miR-153-3p/HIF-1α/Ang-2 axis were evaluated in HUVECs.Results Increased expression of lncRNA-HIF1A-AS2 and decreased expression of miR-153-3p were detected in SBAD tissues.LncRNA-HIF1A-AS2/miR-153-3p/HIF-1αwere upstream regulators of Ang-2,and this axis was involved in angiogenesis in HUVECs.Rifaximin exerted antiangiogenic effects on HUVECs by blocking this axis.Conclusions The lncRNA-HIF1A-AS2/miR-153-3p/HIF-1α/Ang-2 axis is critically involved in SBAD-associated angiogenesis.Rifaximin is a potential therapeutic option for SBAD via blockade of this axis.展开更多
Objective:Several reports have proposed that lnc RNAs,as potential biomarkers,participate in the progression and growth of malignant tumors.HIF1 A-AS2 is a novel lnc RNA and potential biomarker,involved in the genesis...Objective:Several reports have proposed that lnc RNAs,as potential biomarkers,participate in the progression and growth of malignant tumors.HIF1 A-AS2 is a novel lnc RNA and potential biomarker,involved in the genesis and development of carcinomas.However,the molecular mechanism of HIF1 A-AS2 in renal carcinoma is unclear.Methods:The relative expression levels of HIF1 A-AS2 and miR-30 a-5 p were detected using RT-qPCR in renal carcinoma tissues and cell lines.Using loss-of-function and overexpression,the biological effects of HIF1 A-AS2 and miR-30 a-5 p in kidney carcinoma progression were characterized.Dual luciferase reporter gene analysis and Western blot were used to detect the potential mechanism of HIF1 A-AS2 in renal carcinomas.Results:HIF1 A-AS2 was upregulated in kidney carcinoma tissues when compared with para-carcinoma tissues(P<0.05).In addition,tumor size,tumor node mestastasis stage and differentiation were identified as being closely associated with HIF1 A-AS2 expression(P<0.05).Knockdown or overexpression of HIF1 A-AS2 either restrained or promoted the malignant phenotype and WNT/β-catenin signaling in renal carcinoma cells(P<0.05).Mi R-30 a-5 p was downregulated in renal cancers and partially reversed HIF1 A-AS2 functions in malignant renal tumor cells.HIF1 A-AS2 acted as a micro RNA sponge that actively regulated the relative expression of SOX4 in sponging miR-30 a-5 p and subsequently increased the malignant phenotypes of renal carcinomas.HIF1 A-AS2 showed a carcinogenic effect and miR-30 a-5 p acted as an antagonist of the anti-oncogene effects in the pathogenesis of renal carcinomas.Conclusions:The HIF1 A-AS2-miR-30 a-5 p-SOX4 axis was associated with the malignant progression and development of renal carcinoma.The relative expression of HIF1 A-AS2 was negatively correlated with the expression of miR-30 a-5 p,and was closely correlated with SOX4 mRNA levels in renal cancers.展开更多
目的探讨长链非编码RNA(lncRNA)NUTM2B-AS1在口腔鳞状细胞癌组织中的表达及对口腔鳞状细胞癌细胞侵袭和迁移的影响及分子机制。方法采用癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库分析口腔鳞状细胞癌组织和癌旁组织中NUTM2B-...目的探讨长链非编码RNA(lncRNA)NUTM2B-AS1在口腔鳞状细胞癌组织中的表达及对口腔鳞状细胞癌细胞侵袭和迁移的影响及分子机制。方法采用癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库分析口腔鳞状细胞癌组织和癌旁组织中NUTM2B-AS1表达水平。qRT-PCR法检测口腔上皮角质细胞HOK、口腔鳞状细胞癌细胞系Cal-27、SCC-25、SCC-9、HSC-3中NUTM2B-AS1表达水平。Cal-27细胞分别转染NUTM2B-AS1过表达载体(pmirGLO-NUTM2B-AS1)和空载体(pmirGLO),记为NUTM2B-AS1组和对照组,qRT-PCR验证每组细胞中NUTM2B-AS1表达水平。Transwell侵袭实验和细胞划痕实验检测Cal-27细胞侵袭和迁移。生物信息学方法和双荧光素酶报告基因实验验证NUTM2B-AS1和miR-770-5p的靶向关系。qRT-PCR检测Cal-27细胞miR-770-5p的表达,Western blot检测Cal-27细胞Sirt7/Smad4信号通路蛋白(Sirt7、E-cadherin、Smad4、MMP-7、Vimentin)的表达。结果与癌旁组织比较,口腔鳞状细胞癌组织中NUTM2B-AS1表达显著降低(P<0.01)。与HOK细胞比较,口腔鳞状细胞癌细胞系Cal-27、SCC-25、SCC-9、HSC-3中NUTM2B-AS1表达显著降低(P<0.01),Cal-27细胞中NUTM2B-AS1表达最低(P<0.01)。与对照组比较,NUTM2B-AS1组Cal-27细胞中NUTM2B-AS1表达显著升高(P<0.01)。与对照组比较,NUTM2B-AS1组Cal-27细胞侵袭数显著降低(P<0.01),Cal-27细胞划痕愈合率显著降低(P<0.01)。miR-770-5p是NUTM2B-AS1的靶向结合基因(P<0.01)。与对照组相比,NUTM2B-AS1组Cal-27细胞中miR-770-5p表达显著降低(P<0.01),Sirt7、E-cadherin蛋白表达显著升高(P<0.01),Smad4、MMP-7、Vimentin蛋白表达下降(P<0.01)。结论NUTM2B-AS1在口腔鳞状细胞癌组织和细胞系中低表达,高表达NUTM2B-AS1可抑制口腔鳞状细胞癌细胞侵袭和迁移,其作用机制与靶向下调miR-770-5p表达有关。展开更多
基金supported by the Hubei Province Natural ScienceFoundation(No.2022CFC010).
文摘Backgrounds and Objective Angiopoietin-2(Ang-2)is a promising biomarker and therapeutic target for gastrointestinal angiodysplasia(GIAD).We hypothesized that the lncRNA-HIF1A-AS2/miR-153-3p/HIF-1α/Ang-2 axis plays a critical role in small bowel angiodysplasia(SBAD)-associated angiogenesis,which can be blocked by rifaximin.The purpose of this study was to investigate the expression and pro-angiogenic effects of the lncRNA-HIF1A-AS2/miR-153-3p/HIF-1α/Ang-2 in SBAD and to evaluate the therapeutic potential of rifaximin on SBAD by targeting this axis.Methods The expression and pro-angiogenic effects of lncRNA-HIF1A-AS2/miR-153-3p/HIF-1α/Ang-2 were analysed in SBAD tissues and human umbilical vein endothelial cells(HUVECs).The anti-angiogenic effect of rifaximin and its impact on the lncRNA-HIF1A-AS2/miR-153-3p/HIF-1α/Ang-2 axis were evaluated in HUVECs.Results Increased expression of lncRNA-HIF1A-AS2 and decreased expression of miR-153-3p were detected in SBAD tissues.LncRNA-HIF1A-AS2/miR-153-3p/HIF-1αwere upstream regulators of Ang-2,and this axis was involved in angiogenesis in HUVECs.Rifaximin exerted antiangiogenic effects on HUVECs by blocking this axis.Conclusions The lncRNA-HIF1A-AS2/miR-153-3p/HIF-1α/Ang-2 axis is critically involved in SBAD-associated angiogenesis.Rifaximin is a potential therapeutic option for SBAD via blockade of this axis.
基金supported by grants from the National Natural Science Foundations of China(Grant Nos.81702511,81472401,81772708,and 2016YFA0201204)the Jiangsu Provincial Key Medical Discipline(Grant No.ZDXKA2016012)+1 种基金the Clinical Medicine Center of Suzhou(Grant No.SZZXJ201501)programs for Recruitment of Clinical Medical Top Team of Suzhou。
文摘Objective:Several reports have proposed that lnc RNAs,as potential biomarkers,participate in the progression and growth of malignant tumors.HIF1 A-AS2 is a novel lnc RNA and potential biomarker,involved in the genesis and development of carcinomas.However,the molecular mechanism of HIF1 A-AS2 in renal carcinoma is unclear.Methods:The relative expression levels of HIF1 A-AS2 and miR-30 a-5 p were detected using RT-qPCR in renal carcinoma tissues and cell lines.Using loss-of-function and overexpression,the biological effects of HIF1 A-AS2 and miR-30 a-5 p in kidney carcinoma progression were characterized.Dual luciferase reporter gene analysis and Western blot were used to detect the potential mechanism of HIF1 A-AS2 in renal carcinomas.Results:HIF1 A-AS2 was upregulated in kidney carcinoma tissues when compared with para-carcinoma tissues(P<0.05).In addition,tumor size,tumor node mestastasis stage and differentiation were identified as being closely associated with HIF1 A-AS2 expression(P<0.05).Knockdown or overexpression of HIF1 A-AS2 either restrained or promoted the malignant phenotype and WNT/β-catenin signaling in renal carcinoma cells(P<0.05).Mi R-30 a-5 p was downregulated in renal cancers and partially reversed HIF1 A-AS2 functions in malignant renal tumor cells.HIF1 A-AS2 acted as a micro RNA sponge that actively regulated the relative expression of SOX4 in sponging miR-30 a-5 p and subsequently increased the malignant phenotypes of renal carcinomas.HIF1 A-AS2 showed a carcinogenic effect and miR-30 a-5 p acted as an antagonist of the anti-oncogene effects in the pathogenesis of renal carcinomas.Conclusions:The HIF1 A-AS2-miR-30 a-5 p-SOX4 axis was associated with the malignant progression and development of renal carcinoma.The relative expression of HIF1 A-AS2 was negatively correlated with the expression of miR-30 a-5 p,and was closely correlated with SOX4 mRNA levels in renal cancers.
文摘目的探讨长链非编码RNA(lncRNA)NUTM2B-AS1在口腔鳞状细胞癌组织中的表达及对口腔鳞状细胞癌细胞侵袭和迁移的影响及分子机制。方法采用癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库分析口腔鳞状细胞癌组织和癌旁组织中NUTM2B-AS1表达水平。qRT-PCR法检测口腔上皮角质细胞HOK、口腔鳞状细胞癌细胞系Cal-27、SCC-25、SCC-9、HSC-3中NUTM2B-AS1表达水平。Cal-27细胞分别转染NUTM2B-AS1过表达载体(pmirGLO-NUTM2B-AS1)和空载体(pmirGLO),记为NUTM2B-AS1组和对照组,qRT-PCR验证每组细胞中NUTM2B-AS1表达水平。Transwell侵袭实验和细胞划痕实验检测Cal-27细胞侵袭和迁移。生物信息学方法和双荧光素酶报告基因实验验证NUTM2B-AS1和miR-770-5p的靶向关系。qRT-PCR检测Cal-27细胞miR-770-5p的表达,Western blot检测Cal-27细胞Sirt7/Smad4信号通路蛋白(Sirt7、E-cadherin、Smad4、MMP-7、Vimentin)的表达。结果与癌旁组织比较,口腔鳞状细胞癌组织中NUTM2B-AS1表达显著降低(P<0.01)。与HOK细胞比较,口腔鳞状细胞癌细胞系Cal-27、SCC-25、SCC-9、HSC-3中NUTM2B-AS1表达显著降低(P<0.01),Cal-27细胞中NUTM2B-AS1表达最低(P<0.01)。与对照组比较,NUTM2B-AS1组Cal-27细胞中NUTM2B-AS1表达显著升高(P<0.01)。与对照组比较,NUTM2B-AS1组Cal-27细胞侵袭数显著降低(P<0.01),Cal-27细胞划痕愈合率显著降低(P<0.01)。miR-770-5p是NUTM2B-AS1的靶向结合基因(P<0.01)。与对照组相比,NUTM2B-AS1组Cal-27细胞中miR-770-5p表达显著降低(P<0.01),Sirt7、E-cadherin蛋白表达显著升高(P<0.01),Smad4、MMP-7、Vimentin蛋白表达下降(P<0.01)。结论NUTM2B-AS1在口腔鳞状细胞癌组织和细胞系中低表达,高表达NUTM2B-AS1可抑制口腔鳞状细胞癌细胞侵袭和迁移,其作用机制与靶向下调miR-770-5p表达有关。
