我国科学家揭示miRNA对鸡白血病肿瘤的调控机制.doc

我国科学家揭示miRNA对鸡白血病肿瘤的调控机制华南农业大学谢青梅教授领衔团队针对miRNA对鸡白血病的调控进行研究发现，gga-miR-375作为一种肿瘤抑制基因调节癌细胞的增殖并且在鸡白血病肿瘤发生中起着关键的作用。华南农业大学谢青梅教授领衔团队针对miRNA对鸡白血病的调控进行研究发现，gga-miR-375作为一种肿瘤抑制基因调节癌细胞的增殖并且在鸡白血病肿瘤发生中起着关键的作用。相关文章发表于2014年4月2日的PLoS ONE杂志上。J亚群禽白血病病毒(J avian leukosis virus J ，ALV-J)，属于逆转录病毒家族，可以导致鸡白血病及各种肿瘤性疾病发生，在家禽界广泛传播。迄今为止， ALV J在商业型鸡和肉用型鸡的感染对世界各地的家禽业已经造成了重大的经济损失。micrornA(miRNA)一种小的内源性非编码RNA，在肿瘤发生和发展中发挥致癌基因和抑癌基因的关键作用。然而，很少知道miRNA在鸡白血病肿瘤中的潜在作用。为此，华南农业大学谢青梅教授领衔团队针对miRNA对鸡白血病的调控进行研究，成果发表在PLoS ONE上。研究人员首先通过miRNA芯片检测未被侵染的鸡和ALV-J侵染的鸡miRNA的差异表达(芯片服务由联川生物提供)，发现gga-miR-375在患有鸡白血病的鸡中出现下调，并可以靶向YAP1致癌基因抑制细胞增殖。研究人员发现ga-miR-375的过表达对DF-1细胞增殖有明显的抑制作用，并显著降低YES相关蛋白 1(yes-associated protein 1，YAP1)的表达。随后研究人员做了体内实验，发现受感染的鸡肝20天后gga-miR-375发生显著下调，而此时YAP1发生显著上调(P0.05)。研究人员还发现细胞周期蛋白E，细胞周期进程中一个重要的调节因子，它的表达在感染期间发生显著上调(P0.05) 。果蝇细胞凋亡蛋白1抑制剂(DIAP1)，与依赖半胱天冬酶的细胞凋亡有关，在感染后也显著上调。研究结果表明，gga-miR-375作为一种肿瘤抑制基因调节癌细胞的增殖并且在鸡白血病肿瘤发生中起着关键的作用。原文摘要：gga-miR-375 Plays a Key Role in Tumorigenesis Post Subgroup J Avian Leukosis Virus InfectionHongxin Li, HuIQing Shang, Dingming Shu, Huanmin Zhang, Jun Ji, Baoli Sun, Hongmei Li, Qingmei XieAvian leukosis is a neoplastic disease caused in part by subgroup J avian leukosis virus J (ALV-J). Micro ribonucleic acids (miRNAs) play pivotal oncogenic and tumour-suppressor roles in tumour development and progression. However, little is known about the potential role of miRNAs in avian leukosis tumours. We have found a novel tumour-suppressor miRNA, gga-miR-375, associated with avian leukosis tumorigenesis by miRNA microarray in a previous report. We have also previously studied the biological function of gga-miR-375; Overexpression of gga-miR-375 significantly inhibited DF-1 cell proliferation, and significantly reduced the expression of yes-associated protein 1 (YAP1) by repressing the activity of a luciferase reporter carrying the 3-untranslated region of YAP1. This indicates that gga-miR-375 is frequently downregulated in avian leukosis by inhibiting cell proliferation through YAP1 oncogene targeting. Overexpression of gga-miR-375 markedly promoted serum starvation induced apoptosis, and there may be the reason why the tumour cycle is so long in the infected chickens. In vivo assays, gga-miR-375 was significantly downregulated in chicken livers 20 days after infection with ALV-J, and YAP1 was significantly upregulated 20 days after ALV-J infection (P0.05). We also found that expression of cyclin E, an important regulator of cell cycle progression, was significantly upregulated (P0.05). Drosophila inhibitor of apoptosis protein 1 (DIAP1), which is related to caspase-dependent apoptosis, was also significantly upregulated after infection. Our data suggests that gga-miR-