piRNA是一类小的非编码RNA分子,在癌症的发生发展中发挥着重要作用。近年来,piRNA在癌症治疗中的潜力逐渐被挖掘,受到越来越多的关注。本文从piRNA直接发挥治疗作用、协同其他药物增强疗效以及克服耐药三个方面进行分类阐述,探讨piRNA...piRNA是一类小的非编码RNA分子,在癌症的发生发展中发挥着重要作用。近年来,piRNA在癌症治疗中的潜力逐渐被挖掘,受到越来越多的关注。本文从piRNA直接发挥治疗作用、协同其他药物增强疗效以及克服耐药三个方面进行分类阐述,探讨piRNA在癌症临床治疗中的潜在应用价值。通过深入研究piRNA的作用机制,可以为开发新的癌症治疗药物提供理论依据,有望改善癌症患者的治疗效果和生活质量。piRNAs are small non-coding RNAs that play an important role in the initiation and development of cancer. In recent years, the potential of piRNA in cancer therapy has received increasing attention. In this review, the potential application of piRNA in cancer therapy is discussed from three aspects: direct therapeutic effect of piRNA, synergistic effect with other drugs and overcoming drug resistance. The in-depth study on the mechanism of action of piRNA can provide theoretical basis for the development of new cancer treatment drugs and strategies, and is expected to improve the treatment effect and quality of life of cancer patients.展开更多
Carbon black(CB)is a vital constituent of airborne pollutants,comprising diesel exhaust and fine particulate matter(PM_(2.5)),aswell as a prevalent manufacturingmaterial.CBwas known to cause pulmonary dysfunction and ...Carbon black(CB)is a vital constituent of airborne pollutants,comprising diesel exhaust and fine particulate matter(PM_(2.5)),aswell as a prevalent manufacturingmaterial.CBwas known to cause pulmonary dysfunction and fibrosis.However,the detailedmolecular mechanisms underlying fibrosis development are poorly understood.In this study,18 C57BL/6mice were randomized into two groups and exposed to CB and filtered air(FA)for 28 days,with 6 hr/day and 7 days perweek exposure regimen,respectively.The human normal bronchial epithelial cell line(BEAS-2B)was subjected to CB treatment for 24 h in vitro,with CB concentrations in 0,50,100,and 200μg/mL.Our study indicated that exposure to CB resulted in a reduction in lung function and the development of pulmonary fibrosis in mice.Furthermore,our results showed cytoskeleton rearrangement and epithelial-mesenchymal transition(EMT)phenotype in BEAS-2B cells were happened,after CB exposure.Subsequent studies revealed that elevated expression of THBS2 after CB primarily contributed to the development of pulmonary fibrosis.The research findings from both in vivo and in vitro studies provided evidence that piR-713551 was involved in CB exposure-induced EMT by targeting the THBS2 gene and activating theβ-catenin pathway.Mechanically,piR-713551/PIWIL4 complex activated the THBS2 transcription by recruitment of histone demethyltransferase KDM4A to reduce H3K9me3 modification at the THBS2 gene promoter.Conclusively,our research showed that CB exposure could activate EMT and lead pulmonary fibrosis which was modulated by piR-713551/PIWIL4 targeting THBS2.展开更多
文摘目的探究PIWI相互作用RNA(piRNA)在宫颈癌(CC)中的生物学功能和作用机制。方法通过实时荧光定量PCR(RT-qPCR)检测CC组织、CaSki细胞和End1/E6E7细胞中piRNA-2732的表达量;通过EpiQuik m6A RNA甲基化定量试剂盒检测CaSki细胞中N6-甲基腺嘌呤(m6A)RNA的甲基化水平;通过RT-qPCR检测CaSki细胞中甲基转移酶(METTL3,METTL14和WTAP)和去甲基化酶(FTO,ALKBH5)mRNA的表达水平;将CaSki细胞培养至对数生长期后分为6组,piRNA-2732模拟物阴性对照组(mi-NC组)、piRNA-2732模拟物组(mi-2732组)、piRNA-2732抑制剂阴性对照组(in-NC组)、piRNA-2732抑制剂组(in-2732组)、piRNA-2732模拟物+METTL3敲低对照组(mi-2732+si-NC组)和piRNA-2732模拟物+METTL3敲低组(mi-2732+si-METTL3组),通过CCK8检测CaSki细胞的活力;集落形成试验检测CaSki细胞的增殖能力;Transwell实验检测CaSki细胞迁移和侵袭能力;RT-qPCR和蛋白质印迹法(WB)检测甲基转移酶样蛋白3(METTL3)的表达;分别在mi-NC组、mi-2732组、in-NC组和in-2732组中转染METTL3野生型(METTL3-WT)和METTL3突变型(METTL3-MUT),通过双荧光素酶报告基因实验检测piRNA-2732对METTL3的作用。结果与癌旁组织相比,CC患者癌组织中piRNA-2732(3.84±1.08 vs 1.32±0.53)显著高表达,差异具有统计学意义(t=5.115,P<0.001)。与End1/E6E7细胞相比,Caski细胞中piRNA-2732(1.67±0.16 vs 1.00±0.13)的表达显著增高,差异具有统计学意义(t=5.632,P<0.01)。与mi-NC组相比,mi-2732组促进了CaSki细胞活力、增殖、迁移和侵袭能力,差异具有统计学意义(t=4.410~11.040,均P<0.01)。与mi-NC组相比,mi-2732组增加了m6A RNA甲基化水平和METTL3 mRNA及蛋白表达水平,差异具有统计学意义(t=6.176,9.211,12.550,均P<0.05)。双荧光素酶报告基因检测结果显示,与mi-NC+METTL3-WT组相比,mi-2732+METTL3-WT组的相对荧光素酶活性显著增加(t=11.850);与mi-2732+METTL3-WT组相比,mi-2732+METTL3-MUT组的相对荧光素酶活性显著降低(t=12.740),差异具有统计学意义(均P<0.0001)。与in-NC+METTL3-WT组相比,in-2732+METTL3-WT组的相对荧光素酶活性显著降低(t=7.828);与in-2732+METTL3-WT组相比,in-2732+METTL3-MUT组Caski细胞的相对荧光素酶活性显著升高(t=8.146),差异具有统计学意义(均P<0.001)。与mi-2732+si-NC组相比,mi-2732+si-METTL3组Caski的M6A表达水平显著降低,差异具有统计学意义(t=7.630,P<0.01)。与mi-2732+si-NC组相比,mi-2732+si-METTL3组CaSki细胞增殖能力显著下降,细胞集落数显著减少,细胞迁移和侵袭能力显著下降,差异具有统计学意义(t=3.695~4.891,均P<0.001)。结论piRNA-2732在CC组织和细胞中过表达,且piRNA-2732以METTL3介导的m6A甲基化方式促进CC的肿瘤发生。
文摘piRNA是一类小的非编码RNA分子,在癌症的发生发展中发挥着重要作用。近年来,piRNA在癌症治疗中的潜力逐渐被挖掘,受到越来越多的关注。本文从piRNA直接发挥治疗作用、协同其他药物增强疗效以及克服耐药三个方面进行分类阐述,探讨piRNA在癌症临床治疗中的潜在应用价值。通过深入研究piRNA的作用机制,可以为开发新的癌症治疗药物提供理论依据,有望改善癌症患者的治疗效果和生活质量。piRNAs are small non-coding RNAs that play an important role in the initiation and development of cancer. In recent years, the potential of piRNA in cancer therapy has received increasing attention. In this review, the potential application of piRNA in cancer therapy is discussed from three aspects: direct therapeutic effect of piRNA, synergistic effect with other drugs and overcoming drug resistance. The in-depth study on the mechanism of action of piRNA can provide theoretical basis for the development of new cancer treatment drugs and strategies, and is expected to improve the treatment effect and quality of life of cancer patients.
基金supported by the National Natural Science Foundation of China(Nos.81973074,92043202,82204075,and 82204074).
文摘Carbon black(CB)is a vital constituent of airborne pollutants,comprising diesel exhaust and fine particulate matter(PM_(2.5)),aswell as a prevalent manufacturingmaterial.CBwas known to cause pulmonary dysfunction and fibrosis.However,the detailedmolecular mechanisms underlying fibrosis development are poorly understood.In this study,18 C57BL/6mice were randomized into two groups and exposed to CB and filtered air(FA)for 28 days,with 6 hr/day and 7 days perweek exposure regimen,respectively.The human normal bronchial epithelial cell line(BEAS-2B)was subjected to CB treatment for 24 h in vitro,with CB concentrations in 0,50,100,and 200μg/mL.Our study indicated that exposure to CB resulted in a reduction in lung function and the development of pulmonary fibrosis in mice.Furthermore,our results showed cytoskeleton rearrangement and epithelial-mesenchymal transition(EMT)phenotype in BEAS-2B cells were happened,after CB exposure.Subsequent studies revealed that elevated expression of THBS2 after CB primarily contributed to the development of pulmonary fibrosis.The research findings from both in vivo and in vitro studies provided evidence that piR-713551 was involved in CB exposure-induced EMT by targeting the THBS2 gene and activating theβ-catenin pathway.Mechanically,piR-713551/PIWIL4 complex activated the THBS2 transcription by recruitment of histone demethyltransferase KDM4A to reduce H3K9me3 modification at the THBS2 gene promoter.Conclusively,our research showed that CB exposure could activate EMT and lead pulmonary fibrosis which was modulated by piR-713551/PIWIL4 targeting THBS2.
