AIM To investigate micro(mi)R-34 a-antagonizing circular(circ)RNA that underlies hepatocellular steatosis.METHODS The effect of circ RNA on mi R-34 a was recognized by the mi RNA response element(MRE), and validated b...AIM To investigate micro(mi)R-34 a-antagonizing circular(circ)RNA that underlies hepatocellular steatosis.METHODS The effect of circ RNA on mi R-34 a was recognized by the mi RNA response element(MRE), and validated by the dual-luciferase reporter assay. Its association with hepatocellular steatosis was investigated in Hep G2-based hepatocellular steatosis induced by free fatty acids(FFAs; 2:1 oleate:palmitate) stimulation. After normalization of the steatosis-related circRNA by expression vector, analysis of mi R-34 a activity,peroxisome proliferator-activated receptor(PPAR)α level, and expression of downstream genes were carried out so as to reveal its impact on the mi R-34 a/PPARα regulatory system. Both triglyceride(TG) assessment and cytopathological manifestations uncovered the role of circRNA in miR-34 a-dependent hepatosteatogenesis.RESULTS Bioinformatic and functional analysis verified circRNA_0046366 to antagonize the activity of mi R-34 a via MRE-based complementation. In contrast to its lowered level during FFA-induced hepatocellular steatosis, circ RNA_0046366 up-regulation abolished the mi R-34 a-dependent inhibition of PPARα that played a critical role in metabolic signaling pathways. PPARα restoration exerted transcriptional improvement to multiple genes responsible for lipid metabolism. TGspecific lipolytic genes [carnitine palmitoyltransferase 1 A(CPT1 A) and solute-carrier family 27 A(SLC27 A)] among these showed significant increase in their expression levels. The circ RNA_0046366-related rebalancing of lipid homeostasis led to dramatic reduction of TG content, and resulted in the ameliorated phenotype of hepatocellular steatosis.CONCLUSION Dysregulation of circ RNA_0046366/mi R-34 a/PPARα signaling may be a novel epigenetic mechanism underlying hepatocellular steatosis. circ RNA_0046366 serves as a potential target for the treatment of hepatic steatosis.展开更多
BACKGROUND Circular RNAs(circRNAs)are critical regulators in tumorigenesis,functioning as microRNA sponges or protein decoys.Although numerous circRNAs have been implicated in gastric cancer progression,the role of hs...BACKGROUND Circular RNAs(circRNAs)are critical regulators in tumorigenesis,functioning as microRNA sponges or protein decoys.Although numerous circRNAs have been implicated in gastric cancer progression,the role of hsa_circRNA_101996 remains unclear.This study hypothesizes that hsa_circRNA_101996 promotes gastric cancer cell proliferation and apoptosis via the microRNA-577(miR-577)/high mobility group nucleosome binding domain 5(HMGN5)axis.AIM To investigate the role of hsa_circRNA_101996 in gastric cancer proliferation and apoptosis through the miR-577/HMGN5 axis.METHODS Forty-one paired gastric cancer tissues and adjacent non-cancerous tissues were analyzed.Differential circRNA expression was identified using GSE83521 and GSE89143 datasets.miR-577 and HMGN5 were predicted via CircInteractome and TargetScan.Functional experiments(MTT,colony formation,Western blot)and dual-luciferase reporter assays were performed in gastric cancer cell lines(OCUM-1,HSC-39).In vivo tumorigenesis was validated in nude mice.Statistical analysis included Student’s t-test and one-way ANOVA(P<0.05).RESULTS Hsa_circRNA_101996 was significantly upregulated in gastric cancer tissues and cell lines compared to adjacent non-cancerous tissues(P<0.05).Dual-luciferase reporter assays validated the interactions among hsa_circRNA_101996,miR-577,and HMGN5.In vitro,gastric cancer cells overexpressing hsa_circRNA_101996 showed significantly increased proliferation and decreased apoptosis compared to controls(P<0.05).Cells transfected with miR-577 mimics exhibited reduced proliferation and increased apoptosis(P<0.05).Co-transfection with hsa_circRNA_101996 or HMGN5 reversed the effects of miR-577 mimics.In vivo,hsa_circRNA_101996-overexpressing tumors showed increased volume and HMGN5 expression(P<0.05).CONCLUSION Hsa_circRNA_101996 promotes gastric cancer progression by sponging miR-577 to upregulate HMGN5,suggesting a novel therapeutic target for gastric cancer.展开更多
目的探究血浆circRNA_0001445在老年性骨质疏松症(senile osteoporosis,SOP)中的表达情况及其临床意义。方法选取2020年11月至2022年5月于常州市第一人民医院老年科住院的患者为研究对象,应用双能X射线吸收检测法(DXA)测量骨密度(bone m...目的探究血浆circRNA_0001445在老年性骨质疏松症(senile osteoporosis,SOP)中的表达情况及其临床意义。方法选取2020年11月至2022年5月于常州市第一人民医院老年科住院的患者为研究对象,应用双能X射线吸收检测法(DXA)测量骨密度(bone mineral density,BMD)根据BMD结果分为SOP组、骨量减少组及骨量正常组,比较各组间临床资料及circRNA_0001445表达量,采用Pearson相关分析circRNA_0001445与骨密度的的相关性;采用二元Logistic回归分析SOP的危险因素;采用受试者工作特征(ROC)曲线分析circRNA_0001445对SOP的诊断价值;采用配对t检验或配对秩和检验比较SOP治疗前后circRNA_0001445表达量变化。结果共纳入150例患者,每组各50例。SOP组circRNA_0001445表达量(0.58±0.30)明显低于骨量减少组(0.88±0.35)及骨量正常组(1.15±0.62),P<0.001;Pearson相关分析示circRNA_0001445表达量与腰椎BMD(r=0.427,P<0.001)、股骨颈BMD(r=0.363,P<0.001)及髋部BMD(r=0.435,P<0.001)存在正相关;二元Logistic回归示高TC(OR=2.740,95%CI:1.473-5.099)、低BMI(OR=0.674,95%CI:0.543-0.837)及circRNA_0001445(OR=0.019,95%CI:0.002~0.144)是SOP发生的危险因素,P<0.05。ROC曲线分析显示,circRNA_0001445可将SOP组与骨量正常组(AUC=0.810,95%CI:0.728~0.892)、骨量减少组(AUC=0.756,95%CI:0.662~0.849)及非SOP组(AUC=0.783,95%CI:0.706~0.860)区分开来。SOP治疗1年后circRNA_0001445表达量较前升高(1.13±0.61 vs 2.14±0.61),P<0.001。结论circRNA_0001445在SOP中低表达,对SOP的诊断及治疗监测具有一定临床价值。展开更多
目的:探讨circRNA_0016418及circRNA_0017247异常表达对恶性黑色素瘤诊断及其预测淋巴结转移的价值。方法:选取2018年01月至2021年10月我院收治的68例恶性黑色素瘤患者,将其分为淋巴结转移组26例和无淋巴结转移组42例。采用实时荧光定量...目的:探讨circRNA_0016418及circRNA_0017247异常表达对恶性黑色素瘤诊断及其预测淋巴结转移的价值。方法:选取2018年01月至2021年10月我院收治的68例恶性黑色素瘤患者,将其分为淋巴结转移组26例和无淋巴结转移组42例。采用实时荧光定量PCR法检测恶性黑色素瘤组织及正常组织中circRNA_0016418及circRNA_0017247的水平。应用受试者工作特征(receiver operating characteristic, ROC)曲线分析circRNA_0016418及circRNA_0017247异常表达对恶性黑色素瘤诊断及其预测淋巴结转移的价值。Pearson相关分析检测恶性黑色素瘤患者中circRNA_0016418水平与circRNA_0017247水平的相关性。结果:恶性黑色素瘤组织中circRNA_0016418水平(2.64±1.17 vs 0.95±0.36)及circRNA_0017247水平(5.18±2.50 vs 1.52±0.63)均明显高于正常组织(P<0.001)。淋巴结转移组circRNA_0016418水平(3.85±1.72 vs 1.66±0.74)及circRNA_0017247水平(7.16±3.82 vs 3.38±1.54)均明显高于无淋巴结转移组(P<0.001)。ROC曲线显示,circRNA_0016418及circRNA_0017247二者联合诊断恶性黑色素瘤的曲线下面积为0.905(95%CI:0.847~0.964),其灵敏度为92.8%,特异度为83.5%;二者联合预测淋巴结转移的曲线下面积为0.957(95%CI:0.895~0.993),其灵敏度为98.0%,特异度为84.6%。相关分析显示,恶性黑色素瘤患者circRNA_0016418水平与circRNA_0017247水平呈正相关(r=0.802,P<0.001)。结论:恶性黑色素瘤组织中circRNA_0016418及circRNA_0017247水平明显升高,与淋巴结转移有关,二者联合检测对恶性黑色素瘤诊断及其预测淋巴结转移有很好的价值。展开更多
基金National Key Research and Development Plan‘Precision Medicine Research’,No.2017YFSF090203National Natural Science Foundation of China,No.81070346,No.81270492,No.81470859,No.81270491 and No.81470840+2 种基金State Key Development Program for Basic Research of China,No.2012CB517501100 Talents Program,No.XBR2011007hProgram of the Committee of Science and Technology,No.09140903500
文摘AIM To investigate micro(mi)R-34 a-antagonizing circular(circ)RNA that underlies hepatocellular steatosis.METHODS The effect of circ RNA on mi R-34 a was recognized by the mi RNA response element(MRE), and validated by the dual-luciferase reporter assay. Its association with hepatocellular steatosis was investigated in Hep G2-based hepatocellular steatosis induced by free fatty acids(FFAs; 2:1 oleate:palmitate) stimulation. After normalization of the steatosis-related circRNA by expression vector, analysis of mi R-34 a activity,peroxisome proliferator-activated receptor(PPAR)α level, and expression of downstream genes were carried out so as to reveal its impact on the mi R-34 a/PPARα regulatory system. Both triglyceride(TG) assessment and cytopathological manifestations uncovered the role of circRNA in miR-34 a-dependent hepatosteatogenesis.RESULTS Bioinformatic and functional analysis verified circRNA_0046366 to antagonize the activity of mi R-34 a via MRE-based complementation. In contrast to its lowered level during FFA-induced hepatocellular steatosis, circ RNA_0046366 up-regulation abolished the mi R-34 a-dependent inhibition of PPARα that played a critical role in metabolic signaling pathways. PPARα restoration exerted transcriptional improvement to multiple genes responsible for lipid metabolism. TGspecific lipolytic genes [carnitine palmitoyltransferase 1 A(CPT1 A) and solute-carrier family 27 A(SLC27 A)] among these showed significant increase in their expression levels. The circ RNA_0046366-related rebalancing of lipid homeostasis led to dramatic reduction of TG content, and resulted in the ameliorated phenotype of hepatocellular steatosis.CONCLUSION Dysregulation of circ RNA_0046366/mi R-34 a/PPARα signaling may be a novel epigenetic mechanism underlying hepatocellular steatosis. circ RNA_0046366 serves as a potential target for the treatment of hepatic steatosis.
文摘BACKGROUND Circular RNAs(circRNAs)are critical regulators in tumorigenesis,functioning as microRNA sponges or protein decoys.Although numerous circRNAs have been implicated in gastric cancer progression,the role of hsa_circRNA_101996 remains unclear.This study hypothesizes that hsa_circRNA_101996 promotes gastric cancer cell proliferation and apoptosis via the microRNA-577(miR-577)/high mobility group nucleosome binding domain 5(HMGN5)axis.AIM To investigate the role of hsa_circRNA_101996 in gastric cancer proliferation and apoptosis through the miR-577/HMGN5 axis.METHODS Forty-one paired gastric cancer tissues and adjacent non-cancerous tissues were analyzed.Differential circRNA expression was identified using GSE83521 and GSE89143 datasets.miR-577 and HMGN5 were predicted via CircInteractome and TargetScan.Functional experiments(MTT,colony formation,Western blot)and dual-luciferase reporter assays were performed in gastric cancer cell lines(OCUM-1,HSC-39).In vivo tumorigenesis was validated in nude mice.Statistical analysis included Student’s t-test and one-way ANOVA(P<0.05).RESULTS Hsa_circRNA_101996 was significantly upregulated in gastric cancer tissues and cell lines compared to adjacent non-cancerous tissues(P<0.05).Dual-luciferase reporter assays validated the interactions among hsa_circRNA_101996,miR-577,and HMGN5.In vitro,gastric cancer cells overexpressing hsa_circRNA_101996 showed significantly increased proliferation and decreased apoptosis compared to controls(P<0.05).Cells transfected with miR-577 mimics exhibited reduced proliferation and increased apoptosis(P<0.05).Co-transfection with hsa_circRNA_101996 or HMGN5 reversed the effects of miR-577 mimics.In vivo,hsa_circRNA_101996-overexpressing tumors showed increased volume and HMGN5 expression(P<0.05).CONCLUSION Hsa_circRNA_101996 promotes gastric cancer progression by sponging miR-577 to upregulate HMGN5,suggesting a novel therapeutic target for gastric cancer.
文摘目的探究血浆circRNA_0001445在老年性骨质疏松症(senile osteoporosis,SOP)中的表达情况及其临床意义。方法选取2020年11月至2022年5月于常州市第一人民医院老年科住院的患者为研究对象,应用双能X射线吸收检测法(DXA)测量骨密度(bone mineral density,BMD)根据BMD结果分为SOP组、骨量减少组及骨量正常组,比较各组间临床资料及circRNA_0001445表达量,采用Pearson相关分析circRNA_0001445与骨密度的的相关性;采用二元Logistic回归分析SOP的危险因素;采用受试者工作特征(ROC)曲线分析circRNA_0001445对SOP的诊断价值;采用配对t检验或配对秩和检验比较SOP治疗前后circRNA_0001445表达量变化。结果共纳入150例患者,每组各50例。SOP组circRNA_0001445表达量(0.58±0.30)明显低于骨量减少组(0.88±0.35)及骨量正常组(1.15±0.62),P<0.001;Pearson相关分析示circRNA_0001445表达量与腰椎BMD(r=0.427,P<0.001)、股骨颈BMD(r=0.363,P<0.001)及髋部BMD(r=0.435,P<0.001)存在正相关;二元Logistic回归示高TC(OR=2.740,95%CI:1.473-5.099)、低BMI(OR=0.674,95%CI:0.543-0.837)及circRNA_0001445(OR=0.019,95%CI:0.002~0.144)是SOP发生的危险因素,P<0.05。ROC曲线分析显示,circRNA_0001445可将SOP组与骨量正常组(AUC=0.810,95%CI:0.728~0.892)、骨量减少组(AUC=0.756,95%CI:0.662~0.849)及非SOP组(AUC=0.783,95%CI:0.706~0.860)区分开来。SOP治疗1年后circRNA_0001445表达量较前升高(1.13±0.61 vs 2.14±0.61),P<0.001。结论circRNA_0001445在SOP中低表达,对SOP的诊断及治疗监测具有一定临床价值。
文摘目的:探讨circRNA_0016418及circRNA_0017247异常表达对恶性黑色素瘤诊断及其预测淋巴结转移的价值。方法:选取2018年01月至2021年10月我院收治的68例恶性黑色素瘤患者,将其分为淋巴结转移组26例和无淋巴结转移组42例。采用实时荧光定量PCR法检测恶性黑色素瘤组织及正常组织中circRNA_0016418及circRNA_0017247的水平。应用受试者工作特征(receiver operating characteristic, ROC)曲线分析circRNA_0016418及circRNA_0017247异常表达对恶性黑色素瘤诊断及其预测淋巴结转移的价值。Pearson相关分析检测恶性黑色素瘤患者中circRNA_0016418水平与circRNA_0017247水平的相关性。结果:恶性黑色素瘤组织中circRNA_0016418水平(2.64±1.17 vs 0.95±0.36)及circRNA_0017247水平(5.18±2.50 vs 1.52±0.63)均明显高于正常组织(P<0.001)。淋巴结转移组circRNA_0016418水平(3.85±1.72 vs 1.66±0.74)及circRNA_0017247水平(7.16±3.82 vs 3.38±1.54)均明显高于无淋巴结转移组(P<0.001)。ROC曲线显示,circRNA_0016418及circRNA_0017247二者联合诊断恶性黑色素瘤的曲线下面积为0.905(95%CI:0.847~0.964),其灵敏度为92.8%,特异度为83.5%;二者联合预测淋巴结转移的曲线下面积为0.957(95%CI:0.895~0.993),其灵敏度为98.0%,特异度为84.6%。相关分析显示,恶性黑色素瘤患者circRNA_0016418水平与circRNA_0017247水平呈正相关(r=0.802,P<0.001)。结论:恶性黑色素瘤组织中circRNA_0016418及circRNA_0017247水平明显升高,与淋巴结转移有关,二者联合检测对恶性黑色素瘤诊断及其预测淋巴结转移有很好的价值。
