Objective:Circular ribose nudeic acids(circRNAs)are implicated in tumor progression and drug resistance of prostate cancer(PCa).The current work explored the function of circ_0005203(aircTHSD4)in the malignancy and do...Objective:Circular ribose nudeic acids(circRNAs)are implicated in tumor progression and drug resistance of prostate cancer(PCa).The current work explored the function of circ_0005203(aircTHSD4)in the malignancy and docetaxel(DTX)resistance of PCa.Methods:circTHSD4 expression within PCa as well as matched non-carcinoma samples was measured through real time reverse transcription quantitative polymerase chain reaction(RT-qPCR).In addition,a subcellular fraction assay was conducted to determine circTHSD4 subcellular localization within PCa cells.In addition,we performed a Western blot(WB)assay to detect high mobility.group A2 protein(HMGA2)levels.Besides,functional associations of two molecules were investigated through dual luciferase reporter assay.Cell Counting Kit(CCK)-8,colony formation together with Transwell assay was conducted to assess malignant phenotypes of PCa cells,whereas flow cytometry was performed to determine cell apoptosis.Furthermore,a xenograft mouse model was constructed to verify the effect of circTHSD4 on the carcinogenesis of PCa cells.Results:According to RT-qPCR results,circTHSD4 was up-regulated within PCa tissues and cells,which predicted the dismal prognostic outcome of PCa cases.circTHSD4 silencing within PCa cells markedly suppressed cell growth,migration,and colony fomation.circTHSD4 silencing remarkably elevated PCa cell apoptosis and carcinogenesis within the xenograft model.Further,circTHSD4 silencing enhanced docetaxel(DTX)sensitivity in PCa cells.Furthermore,we demonstrated that circTHSD4 modulated the malignancy of PCa cells by regulating HMGA2 expression through sponging miR 203.Conclusion:Together,our findings suggest that cirCTHSD4 overexpression could promote the malignant phenotype and DTX resistance in PCa through the regulation of the miR 203/HMGA2 axis.展开更多
目的:探讨肝细胞癌(HCC)患者血清及癌组织中miR-203a和其靶基因的表达及其与患者临床病理特征和预后的关系。方法:利用生物信息学方法从TargetScan、miRDB和PicTar网站预测HCC组织中miR-203a的靶基因,通过双荧光素酶报告基因实验进行验...目的:探讨肝细胞癌(HCC)患者血清及癌组织中miR-203a和其靶基因的表达及其与患者临床病理特征和预后的关系。方法:利用生物信息学方法从TargetScan、miRDB和PicTar网站预测HCC组织中miR-203a的靶基因,通过双荧光素酶报告基因实验进行验证。选取2018年1月至2019年6月在常州市金坛区第二人民医院手术切除的96例HCC患者的癌和癌旁组织标本、血清和临床资料,以及90例健康体检者的血清作为对照。qPCR法检测血清miR-203a水平,以及HCC组织和癌旁组织中miR-203a及其靶基因表达,比较分析不同临床病理特征HCC患者miR-203a及其靶基因表达。随访3年,采用Kaplan-Meier法进行生存(OS)分析。结果:从数据库筛选出HCC中miR-203a相关的靶基因共10个,包括APC、CDK6、GATA6、HOXD3、IGF1R、IGFBP5、KCNE2、PAQR3、PRMT5和SOSC3。HCC组织中mi R-203a和APC、PAQR3 mRNA表达水平均显著低于癌旁组织(均P<0.01),CDK6、GATA6、HOXD3、IGF1R、IGFBP5、KCNE2、PRMT5和SOSC3 m RNA表达水平均显著高于癌旁组织(均P<0.01);血清miR-203a、HCC组织miR-203a及其靶基因表达均与患者肿瘤临床分期、分化程度、肝功能分级、OS率有关(均P<0.01)。结论:HCC组织中miR-203a呈低表达,miR-203a及靶基因表达均与患者肿瘤临床分期、分化程度、肝功能及远期OS率有关。展开更多
基金Fujian Provincial Health and Middleaged and Young Backbone Talents Training Project“The role and Mechanism of C53 in mcRPC Treatment of Drug Resistance”(2019-ZQN-77).
文摘Objective:Circular ribose nudeic acids(circRNAs)are implicated in tumor progression and drug resistance of prostate cancer(PCa).The current work explored the function of circ_0005203(aircTHSD4)in the malignancy and docetaxel(DTX)resistance of PCa.Methods:circTHSD4 expression within PCa as well as matched non-carcinoma samples was measured through real time reverse transcription quantitative polymerase chain reaction(RT-qPCR).In addition,a subcellular fraction assay was conducted to determine circTHSD4 subcellular localization within PCa cells.In addition,we performed a Western blot(WB)assay to detect high mobility.group A2 protein(HMGA2)levels.Besides,functional associations of two molecules were investigated through dual luciferase reporter assay.Cell Counting Kit(CCK)-8,colony formation together with Transwell assay was conducted to assess malignant phenotypes of PCa cells,whereas flow cytometry was performed to determine cell apoptosis.Furthermore,a xenograft mouse model was constructed to verify the effect of circTHSD4 on the carcinogenesis of PCa cells.Results:According to RT-qPCR results,circTHSD4 was up-regulated within PCa tissues and cells,which predicted the dismal prognostic outcome of PCa cases.circTHSD4 silencing within PCa cells markedly suppressed cell growth,migration,and colony fomation.circTHSD4 silencing remarkably elevated PCa cell apoptosis and carcinogenesis within the xenograft model.Further,circTHSD4 silencing enhanced docetaxel(DTX)sensitivity in PCa cells.Furthermore,we demonstrated that circTHSD4 modulated the malignancy of PCa cells by regulating HMGA2 expression through sponging miR 203.Conclusion:Together,our findings suggest that cirCTHSD4 overexpression could promote the malignant phenotype and DTX resistance in PCa through the regulation of the miR 203/HMGA2 axis.
文摘目的:探讨肝细胞癌(HCC)患者血清及癌组织中miR-203a和其靶基因的表达及其与患者临床病理特征和预后的关系。方法:利用生物信息学方法从TargetScan、miRDB和PicTar网站预测HCC组织中miR-203a的靶基因,通过双荧光素酶报告基因实验进行验证。选取2018年1月至2019年6月在常州市金坛区第二人民医院手术切除的96例HCC患者的癌和癌旁组织标本、血清和临床资料,以及90例健康体检者的血清作为对照。qPCR法检测血清miR-203a水平,以及HCC组织和癌旁组织中miR-203a及其靶基因表达,比较分析不同临床病理特征HCC患者miR-203a及其靶基因表达。随访3年,采用Kaplan-Meier法进行生存(OS)分析。结果:从数据库筛选出HCC中miR-203a相关的靶基因共10个,包括APC、CDK6、GATA6、HOXD3、IGF1R、IGFBP5、KCNE2、PAQR3、PRMT5和SOSC3。HCC组织中mi R-203a和APC、PAQR3 mRNA表达水平均显著低于癌旁组织(均P<0.01),CDK6、GATA6、HOXD3、IGF1R、IGFBP5、KCNE2、PRMT5和SOSC3 m RNA表达水平均显著高于癌旁组织(均P<0.01);血清miR-203a、HCC组织miR-203a及其靶基因表达均与患者肿瘤临床分期、分化程度、肝功能分级、OS率有关(均P<0.01)。结论:HCC组织中miR-203a呈低表达,miR-203a及靶基因表达均与患者肿瘤临床分期、分化程度、肝功能及远期OS率有关。
