A major problem which is poorly understood in the management of bladder cancer is low sensitivity to chemotherapy and high recurrence after transurethral resection. Insulin-like growth factor 1 receptor (IGF-1R) signa...A major problem which is poorly understood in the management of bladder cancer is low sensitivity to chemotherapy and high recurrence after transurethral resection. Insulin-like growth factor 1 receptor (IGF-1R) signaling plays a very important role in progression, invasion and metastasis of bladder cancer cells. In this study, we investigated whether IGF-1R was involved in the growth stimulating activity and drug resistance of bladder cancer cells. The results showed: The mRNAs of IGF-1, IGF-2 and IGF-1R were strongly expressed in serum-free cultured T24 cell line, whereas normal urothelial cells did not express these factors/receptors or only in trace leve1s; T24 cell responded far better to growth stimulation by IGF-1 than did normal urothelial cells; blockage of IGF1R by antisense oligodeoxynucleotide (ODN) significantly inhibited the growth of T24 cell and enhanced sensitivity and apoptosis of T24 cells to mitomycin (MMC). These results suggested that blockage of IGF-IR signaling might potentially contribute to the treatment of bladder cancer cells which are insensitive to chemotherapy.展开更多
Controlled gene regulation during gamete development is vital for maintaining reproductive potential. During the complex process of mammalian spermatogenesis, male germ cells experience extended periods of the inactiv...Controlled gene regulation during gamete development is vital for maintaining reproductive potential. During the complex process of mammalian spermatogenesis, male germ cells experience extended periods of the inactive transcription despite heavy translational requirements for continued growth and differentiation. Hence, spermatogenesis is highly reliant on mechanisms of posttranscriptional regulation of gene expression, facilitated by RNA binding proteins （RBPs）, which remain abundantly expressed throughout this process. One such group of proteins is the Musashi family, previously identified as critical regulators of testis germ cell development and meiosis in Drosophila, and also shown to be vital to sperm development and reproductive potential in the mouse. This review describes the role and function of RBPs our recent knowledge of the Musashi proteins in spermatogenesis. within the scope of male germ cell development, focusing on The functional mechanisms utilized by RBPs within the cell are outlined in depth, and the significance of sub-cellular localization and stage-specific expression in relation to the mode and impact of posttranscriptional regulation is also highlighted. We emphasize the historical role of the Musashi family of RBPs in stem cell function and cell fate determination, as originally characterized in Drosophila and Xenopus, and conclude with our current understanding of the differential roles and functions of the mammalian Musashi proteins, Musashi-1 and Musashi-2, with a primary focus on our findings in spermatogenesis. This review highlights both the essential contribution of RBPs to posttranscriptional regulation and the importance of the Musashi family as master regulators of male gamete development.展开更多
目的探讨结肠癌组织中长链非编码RNA(lncRNA)肿瘤蛋白翻译调节因子1(TPT1)-反义RNA1(AS1)、微小RNA(miR)-30c-5p的表达及与病理特征、预后的关系。方法选取2015年1月至2017年12月深圳大学附属第一医院收治的117例接受根治性或姑息性手...目的探讨结肠癌组织中长链非编码RNA(lncRNA)肿瘤蛋白翻译调节因子1(TPT1)-反义RNA1(AS1)、微小RNA(miR)-30c-5p的表达及与病理特征、预后的关系。方法选取2015年1月至2017年12月深圳大学附属第一医院收治的117例接受根治性或姑息性手术切除结肠癌患者,均行手术切除结肠癌组织及癌旁组织。采用qRT-PCR检测lncRNA TPT1-AS1、miR-30c-5p表达水平,分析lncRNA TPT1-AS1、miR-30c-5p表达水平与结肠癌病理特征的关系,采用Pearson相关性检验分析结肠癌组织中lncRNA TPT1-AS1与miR-30c-5p表达水平的相关性,Kaplan-Meier曲线绘制不同lncRNA TPT1-AS1、miR-30c-5p表达水平结肠癌患者3年累积生存率,Cox回归分析结肠癌患者预后影响因素。结果结肠癌组织中lncRNA TPT1-AS1表达水平明显高于癌旁组织(3.405±0.555 vs 1.766±0.096),miR-30c-5p表达水平(0.306±0.146 vs 0.872±0.267)明显低于癌旁组织(P<0.05)。结肠癌lncRNA TPT1-AS1表达水平TNM分期Ⅲ~Ⅳ期明显高于Ⅰ~Ⅱ期(3.651±0.579 vs 3.257±0.486),浸润深度T_(3)~T_(4)明显高于T_(1)~T_(2)(3.523±0.601 vs 3.301±0.491),有淋巴结转移明显高于无淋巴结转移(3.614±0.585 vs 3.220±0.456),差异均有统计学意义(P<0.05);miR-30c-5p表达水平TNM分期Ⅲ~Ⅳ期明显低于Ⅰ~Ⅱ期(0.251±0.126 vs 0.346±0.145),浸润深度T_(3)~T_(4)明显低于T_(1)~T_(2)(0.270±0.119 vs 0.338±0.162),有淋巴结转移明显低于无淋巴结转移(0.255±0.125 vs 0.351±0.151),差异均有统计学意义(P<0.05)。Pearson相关性分析显示,结肠癌组织中lncRNA TPT1-AS1与miR-30c-5p表达水平呈负相关(r=-0.572,P<0.05)。Kaplan-Meier生存曲线显示,lncRNA TPT1-AS1高表达水平组3年累积生存率明显低于低表达水平组(59.32%vs 87.93%),miR-30c-5p高表达水平组3年累积生存率明显高于低表达水平组(85.00%vs 61.40%)(P<0.05)。多因素Cox回归分析显示,TNM分期Ⅲ~Ⅳ期(HR=2.387,95%CI:1.004~5.671)、淋巴结转移(HR=2.667,95%CI:1.021~6.969)、lncRNA TPT1-AS1≥3.405(HR=2.023,95%CI:1.076~3.803)为结肠癌患者预后独立风险因素,miR-30c-5p≥0.306(HR=0.175,95%CI:0.012~0.423)为独立保护因素(P<0.05)。结论结肠癌组织中lncRNA TPT1-AS1表达显著上调,miR-30c-5p表达显著下调,两者与TNM分期、浸润深度、淋巴结转移相关,为患者预后独立影响因素,可能成为结肠癌预后评估的标志物。展开更多
文摘A major problem which is poorly understood in the management of bladder cancer is low sensitivity to chemotherapy and high recurrence after transurethral resection. Insulin-like growth factor 1 receptor (IGF-1R) signaling plays a very important role in progression, invasion and metastasis of bladder cancer cells. In this study, we investigated whether IGF-1R was involved in the growth stimulating activity and drug resistance of bladder cancer cells. The results showed: The mRNAs of IGF-1, IGF-2 and IGF-1R were strongly expressed in serum-free cultured T24 cell line, whereas normal urothelial cells did not express these factors/receptors or only in trace leve1s; T24 cell responded far better to growth stimulation by IGF-1 than did normal urothelial cells; blockage of IGF1R by antisense oligodeoxynucleotide (ODN) significantly inhibited the growth of T24 cell and enhanced sensitivity and apoptosis of T24 cells to mitomycin (MMC). These results suggested that blockage of IGF-IR signaling might potentially contribute to the treatment of bladder cancer cells which are insensitive to chemotherapy.
文摘Controlled gene regulation during gamete development is vital for maintaining reproductive potential. During the complex process of mammalian spermatogenesis, male germ cells experience extended periods of the inactive transcription despite heavy translational requirements for continued growth and differentiation. Hence, spermatogenesis is highly reliant on mechanisms of posttranscriptional regulation of gene expression, facilitated by RNA binding proteins （RBPs）, which remain abundantly expressed throughout this process. One such group of proteins is the Musashi family, previously identified as critical regulators of testis germ cell development and meiosis in Drosophila, and also shown to be vital to sperm development and reproductive potential in the mouse. This review describes the role and function of RBPs our recent knowledge of the Musashi proteins in spermatogenesis. within the scope of male germ cell development, focusing on The functional mechanisms utilized by RBPs within the cell are outlined in depth, and the significance of sub-cellular localization and stage-specific expression in relation to the mode and impact of posttranscriptional regulation is also highlighted. We emphasize the historical role of the Musashi family of RBPs in stem cell function and cell fate determination, as originally characterized in Drosophila and Xenopus, and conclude with our current understanding of the differential roles and functions of the mammalian Musashi proteins, Musashi-1 and Musashi-2, with a primary focus on our findings in spermatogenesis. This review highlights both the essential contribution of RBPs to posttranscriptional regulation and the importance of the Musashi family as master regulators of male gamete development.
文摘目的探讨结肠癌组织中长链非编码RNA(lncRNA)肿瘤蛋白翻译调节因子1(TPT1)-反义RNA1(AS1)、微小RNA(miR)-30c-5p的表达及与病理特征、预后的关系。方法选取2015年1月至2017年12月深圳大学附属第一医院收治的117例接受根治性或姑息性手术切除结肠癌患者,均行手术切除结肠癌组织及癌旁组织。采用qRT-PCR检测lncRNA TPT1-AS1、miR-30c-5p表达水平,分析lncRNA TPT1-AS1、miR-30c-5p表达水平与结肠癌病理特征的关系,采用Pearson相关性检验分析结肠癌组织中lncRNA TPT1-AS1与miR-30c-5p表达水平的相关性,Kaplan-Meier曲线绘制不同lncRNA TPT1-AS1、miR-30c-5p表达水平结肠癌患者3年累积生存率,Cox回归分析结肠癌患者预后影响因素。结果结肠癌组织中lncRNA TPT1-AS1表达水平明显高于癌旁组织(3.405±0.555 vs 1.766±0.096),miR-30c-5p表达水平(0.306±0.146 vs 0.872±0.267)明显低于癌旁组织(P<0.05)。结肠癌lncRNA TPT1-AS1表达水平TNM分期Ⅲ~Ⅳ期明显高于Ⅰ~Ⅱ期(3.651±0.579 vs 3.257±0.486),浸润深度T_(3)~T_(4)明显高于T_(1)~T_(2)(3.523±0.601 vs 3.301±0.491),有淋巴结转移明显高于无淋巴结转移(3.614±0.585 vs 3.220±0.456),差异均有统计学意义(P<0.05);miR-30c-5p表达水平TNM分期Ⅲ~Ⅳ期明显低于Ⅰ~Ⅱ期(0.251±0.126 vs 0.346±0.145),浸润深度T_(3)~T_(4)明显低于T_(1)~T_(2)(0.270±0.119 vs 0.338±0.162),有淋巴结转移明显低于无淋巴结转移(0.255±0.125 vs 0.351±0.151),差异均有统计学意义(P<0.05)。Pearson相关性分析显示,结肠癌组织中lncRNA TPT1-AS1与miR-30c-5p表达水平呈负相关(r=-0.572,P<0.05)。Kaplan-Meier生存曲线显示,lncRNA TPT1-AS1高表达水平组3年累积生存率明显低于低表达水平组(59.32%vs 87.93%),miR-30c-5p高表达水平组3年累积生存率明显高于低表达水平组(85.00%vs 61.40%)(P<0.05)。多因素Cox回归分析显示,TNM分期Ⅲ~Ⅳ期(HR=2.387,95%CI:1.004~5.671)、淋巴结转移(HR=2.667,95%CI:1.021~6.969)、lncRNA TPT1-AS1≥3.405(HR=2.023,95%CI:1.076~3.803)为结肠癌患者预后独立风险因素,miR-30c-5p≥0.306(HR=0.175,95%CI:0.012~0.423)为独立保护因素(P<0.05)。结论结肠癌组织中lncRNA TPT1-AS1表达显著上调,miR-30c-5p表达显著下调,两者与TNM分期、浸润深度、淋巴结转移相关,为患者预后独立影响因素,可能成为结肠癌预后评估的标志物。
