Objective To investigate the expression of programmed cell death 5 （PDCD5） in tissues of normal human prostate （NP）, benign prostatic hyperplasia （BPH）, and prostate cancer （PCa） in order to assess the clinica...Objective To investigate the expression of programmed cell death 5 （PDCD5） in tissues of normal human prostate （NP）, benign prostatic hyperplasia （BPH）, and prostate cancer （PCa） in order to assess the clinical role of PDCD5 in PCa. Methods PDCD5 expression was determined by EnVision immunohistochemical staining in forma-lin-fixed and paraffin-embedded specimens obtained from 12 subjects with NP, 22 with BPH, and 22 with PCa. In addition, PCa cases were classified as low/middle-risk （Gleason sumS7） and high-risk （Gleason sum〉7） on the basis of Gleason grade. Positive expression rates and intensity of PDCD5 protein were observed under light microscope and analyzed with computer imaging technique. Expression of PDCD5 was compared among different prostatic tissues. Results The expression of PDCD5 was significantly lower in tissue of PCa than in tissues of NP and BPH （P〈0.01）. However, there was no significant difference in PDCD5 expression between tissues of NP and BPH. In addition, the expression of PDCD5 was further downregulated with the increase of Gleason sum in PCa. Conclusions By downregulating apoptosis, low PDCD5 expression may play an important role in the occurrence and development of PCa. PDCD5 is supposed to have a potential clinical value to be a new predictor of progression and target of gene therapy in PCa.展开更多
BACKGROUND Anti-programmed death therapy has thrust immunotherapy into the spotlight.However,such therapy has a modest response in hepatocellular carcinoma(HCC).Epigenetic immunomodulation is a suggestive combinatoria...BACKGROUND Anti-programmed death therapy has thrust immunotherapy into the spotlight.However,such therapy has a modest response in hepatocellular carcinoma(HCC).Epigenetic immunomodulation is a suggestive combinatorial therapy with immune checkpoint blockade.Non-coding ribonucleic acid(ncRNA)driven regulation is a major mechanism of epigenetic modulation.Given the wide range of ncRNAs that co-opt in programmed cell-death protein 1(PD-1)/programmed death ligand 1(PD-L1)regulation,and based on the literature,we hypothesized that miR-155-5p,miR-194-5p and long non-coding RNAs(lncRNAs)X-inactive specific transcript(XIST)and MALAT-1 are involved in a regulatory upstream pathway for PD-1/PD-L1.Recently,nutraceutical therapeutics in cancers have received increasing attention.Thus,it is interesting to study the impact of oleuropein on the respective study key players.AIM To explore potential upstream regulatory ncRNAs for the immune checkpoint PD-1/PD-L1.METHODS Bioinformatics tools including microrna.org and lnCeDB software were adopted to detect targeting of miR-155-5p,miR-194-5p and lncRNAs XIST and MALAT-1 to PD-L1 mRNA,respectively.In addition,Diana tool was used to predict targeting of both aforementioned miRNAs to lncRNAs XIST and MALAT-1.HCC and normal tissue samples were collected for scanning of PD-L1,XIST and MALAT-1 expression.To study the interaction among miR-155-5p,miR-194-5p,lncRNAs XIST and MALAT-1,as well as PD-L1 mRNA,a series of transfections of the Huh-7 cell line was carried out.RESULTS Bioinformatics software predicted that miR-155-5p and miR-194-5p can target PDL1,MALAT-1 and XIST.MALAT-1 and XIST were predicted to target PD-L1 mRNA.PD-L1 and XIST were significantly upregulated in 23 HCC biopsies compared to healthy controls;however,MALAT-1 was barely detected.MiR-194 induced expression elevated the expression of PD-L1,XIST and MALAT-1.However,overexpression of miR-155-5p induced the upregulation of PD-L1 and XIST,while it had a negative impact on MALAT-1 expression.Knockdown of XIST did have an impact on PD-L1 expression;however,following knockdown of the negative regulator of X-inactive specific transcript(TSIX),PD-L1 expression was elevated,and abolished MALAT-1 activity.Upon co-transfection of miR-194-5p with siMALAT-1,PD-L1 expression was elevated.Co-transfection of miR-194-5p with siXIST did not have an impact on PD-L1 expression.Upon co-transfection of miR-194 with siTSIX,PD-L1 expression was upregulated.Interestingly,the same PD-L1 expression pattern was observed following miR-155-5p cotransfections.Oleuropein treatment of Huh-7 cells reduced the expression profile of PD-L1,XIST,and miR-155-5p,upregulated the expression of miR-194-5p and had no significant impact on the MALAT-1 expression profile.CONCLUSION This study reported a novel finding revealing that opposing acting miRNAs in HCC,have the same impact on PD-1/PD-L1 immune checkpoint by sharing a common signaling pathway.展开更多
目的:分析新凋亡促进因子-程序化细胞死亡分子5(programmed cell death 5,PDCD5)在肝细胞癌(hepatocellular carcinoma,HCC)发生发展中的作用.方法:用免疫组织化学法(immunohisto-chemistry,IHC)检测40例HCC及其癌旁组织(包括24例肝硬化...目的:分析新凋亡促进因子-程序化细胞死亡分子5(programmed cell death 5,PDCD5)在肝细胞癌(hepatocellular carcinoma,HCC)发生发展中的作用.方法:用免疫组织化学法(immunohisto-chemistry,IHC)检测40例HCC及其癌旁组织(包括24例肝硬化和16例慢性肝炎)中的PDCD5和Fas蛋白表达.用等级资料Kruskal-WallisH检验方法进行统计学分析,并用Spearman's等级资料的相关分析比较PDCD5和Fas的表达差异.结果:PDCD5在肝癌组织中多呈阴性表达,在癌旁肝组织中表达增加.肝癌及其癌旁肝硬化肝炎各组间PDCD5表达具有显著性差异(χ2=46.03,P=0.000).Fas在肝癌组织及其癌旁肝硬化或慢性肝炎组织中的表达分布与PDCD5相似,各组间Fas表达有显著性差异(χ2=24.45P=0.000).PDCD5与Fas的相关性分析结果显示,两者呈正相关(r=0.839,P=0.001).结论:PDCD5是HCC发生、发展过程中的一个重要凋亡调控因子.展开更多
目的:探讨在子宫内膜癌细胞中重组人程序性细胞死亡蛋白5(recombinant human programmed cell death protein 5,rhPDCD5)对紫杉醇化疗的促进作用。方法:子宫内膜癌KLE细胞培养完成后,通过重组人rh PDCD5(20μg/ml)处理KLE细胞,再分别以0...目的:探讨在子宫内膜癌细胞中重组人程序性细胞死亡蛋白5(recombinant human programmed cell death protein 5,rhPDCD5)对紫杉醇化疗的促进作用。方法:子宫内膜癌KLE细胞培养完成后,通过重组人rh PDCD5(20μg/ml)处理KLE细胞,再分别以0、1.0、5.0、10.0、50μmol/L紫杉醇(paclitaxel,PTX)处理24 h或以10μmol/L PTX处理0、12、24、48 h,提取细胞总RNA及蛋白后,CCK法检测KLE细胞的增殖情况,流式细胞术检测KLE细胞凋亡情况,实时定量PCR检测KLE细胞中PDCD5mRNA的表达量,实时定量PCR或Western blotting测定凋亡相关基因的Bax、Bcl2、caspase-3 mRNA或蛋白水平的变化。结果:PTX对PDCD5表达的促进作用具有剂量依赖性和时间依赖性;PTX的最佳作用浓度为10μmol/L,最佳作用时间为24 h。rh PDCD5明显增强紫杉醇对KLE细胞的抑制作用。CCK实验、流式细胞术及Western blotting检测显示:PTX+rhPDCD5联合处理组KLE细胞的增殖抑制率和凋亡率均较PTX组明显增加、pro-caspase 3的表达量明显增加(均P<0.01)。促进凋亡蛋白Bax和抑制凋亡蛋白Bcl2的比值亦较明显增加(P<0.01)。结论:rhPDCD5可协同PTX抑制子宫内膜癌KLE细胞的增殖、促进细胞的凋亡,可明显增强KLE细胞对PTX的药物敏感性。展开更多
文摘Objective To investigate the expression of programmed cell death 5 （PDCD5） in tissues of normal human prostate （NP）, benign prostatic hyperplasia （BPH）, and prostate cancer （PCa） in order to assess the clinical role of PDCD5 in PCa. Methods PDCD5 expression was determined by EnVision immunohistochemical staining in forma-lin-fixed and paraffin-embedded specimens obtained from 12 subjects with NP, 22 with BPH, and 22 with PCa. In addition, PCa cases were classified as low/middle-risk （Gleason sumS7） and high-risk （Gleason sum〉7） on the basis of Gleason grade. Positive expression rates and intensity of PDCD5 protein were observed under light microscope and analyzed with computer imaging technique. Expression of PDCD5 was compared among different prostatic tissues. Results The expression of PDCD5 was significantly lower in tissue of PCa than in tissues of NP and BPH （P〈0.01）. However, there was no significant difference in PDCD5 expression between tissues of NP and BPH. In addition, the expression of PDCD5 was further downregulated with the increase of Gleason sum in PCa. Conclusions By downregulating apoptosis, low PDCD5 expression may play an important role in the occurrence and development of PCa. PDCD5 is supposed to have a potential clinical value to be a new predictor of progression and target of gene therapy in PCa.
文摘BACKGROUND Anti-programmed death therapy has thrust immunotherapy into the spotlight.However,such therapy has a modest response in hepatocellular carcinoma(HCC).Epigenetic immunomodulation is a suggestive combinatorial therapy with immune checkpoint blockade.Non-coding ribonucleic acid(ncRNA)driven regulation is a major mechanism of epigenetic modulation.Given the wide range of ncRNAs that co-opt in programmed cell-death protein 1(PD-1)/programmed death ligand 1(PD-L1)regulation,and based on the literature,we hypothesized that miR-155-5p,miR-194-5p and long non-coding RNAs(lncRNAs)X-inactive specific transcript(XIST)and MALAT-1 are involved in a regulatory upstream pathway for PD-1/PD-L1.Recently,nutraceutical therapeutics in cancers have received increasing attention.Thus,it is interesting to study the impact of oleuropein on the respective study key players.AIM To explore potential upstream regulatory ncRNAs for the immune checkpoint PD-1/PD-L1.METHODS Bioinformatics tools including microrna.org and lnCeDB software were adopted to detect targeting of miR-155-5p,miR-194-5p and lncRNAs XIST and MALAT-1 to PD-L1 mRNA,respectively.In addition,Diana tool was used to predict targeting of both aforementioned miRNAs to lncRNAs XIST and MALAT-1.HCC and normal tissue samples were collected for scanning of PD-L1,XIST and MALAT-1 expression.To study the interaction among miR-155-5p,miR-194-5p,lncRNAs XIST and MALAT-1,as well as PD-L1 mRNA,a series of transfections of the Huh-7 cell line was carried out.RESULTS Bioinformatics software predicted that miR-155-5p and miR-194-5p can target PDL1,MALAT-1 and XIST.MALAT-1 and XIST were predicted to target PD-L1 mRNA.PD-L1 and XIST were significantly upregulated in 23 HCC biopsies compared to healthy controls;however,MALAT-1 was barely detected.MiR-194 induced expression elevated the expression of PD-L1,XIST and MALAT-1.However,overexpression of miR-155-5p induced the upregulation of PD-L1 and XIST,while it had a negative impact on MALAT-1 expression.Knockdown of XIST did have an impact on PD-L1 expression;however,following knockdown of the negative regulator of X-inactive specific transcript(TSIX),PD-L1 expression was elevated,and abolished MALAT-1 activity.Upon co-transfection of miR-194-5p with siMALAT-1,PD-L1 expression was elevated.Co-transfection of miR-194-5p with siXIST did not have an impact on PD-L1 expression.Upon co-transfection of miR-194 with siTSIX,PD-L1 expression was upregulated.Interestingly,the same PD-L1 expression pattern was observed following miR-155-5p cotransfections.Oleuropein treatment of Huh-7 cells reduced the expression profile of PD-L1,XIST,and miR-155-5p,upregulated the expression of miR-194-5p and had no significant impact on the MALAT-1 expression profile.CONCLUSION This study reported a novel finding revealing that opposing acting miRNAs in HCC,have the same impact on PD-1/PD-L1 immune checkpoint by sharing a common signaling pathway.
文摘目的:分析新凋亡促进因子-程序化细胞死亡分子5(programmed cell death 5,PDCD5)在肝细胞癌(hepatocellular carcinoma,HCC)发生发展中的作用.方法:用免疫组织化学法(immunohisto-chemistry,IHC)检测40例HCC及其癌旁组织(包括24例肝硬化和16例慢性肝炎)中的PDCD5和Fas蛋白表达.用等级资料Kruskal-WallisH检验方法进行统计学分析,并用Spearman's等级资料的相关分析比较PDCD5和Fas的表达差异.结果:PDCD5在肝癌组织中多呈阴性表达,在癌旁肝组织中表达增加.肝癌及其癌旁肝硬化肝炎各组间PDCD5表达具有显著性差异(χ2=46.03,P=0.000).Fas在肝癌组织及其癌旁肝硬化或慢性肝炎组织中的表达分布与PDCD5相似,各组间Fas表达有显著性差异(χ2=24.45P=0.000).PDCD5与Fas的相关性分析结果显示,两者呈正相关(r=0.839,P=0.001).结论:PDCD5是HCC发生、发展过程中的一个重要凋亡调控因子.
