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Cancer Cell:外泌体携带长链非编码RNA传播肾癌细胞对靶向药物耐药

2016-05-17 Lin-Hui Wang 《肿瘤细胞》

如果把传统的放化疗比作“万箭齐发、狂轰滥炸”,那么靶向治疗即为“精确制导、定点清除”。晚期肾癌患者希望实施靶向治疗,却一直缺乏标志物而“无靶可打”。第二军医大学长征医院泌尿外科王林辉课题组与东方肝胆外科医院生物信号转导实验室主任王红阳院士研究组合作,发现了一条介导肾癌靶向药物耐药形成的新型长链非编码RNA,可作为预测靶向药物治疗疗效的分子标志物和逆转靶向药物耐药的干预靶点,使晚期肾癌患者接受更加精

如果把传统的放化疗比作“万箭齐发、狂轰滥炸”,那么靶向治疗即为“精确制导、定点清除”。晚期肾癌患者希望实施靶向治疗,却一直缺乏标志物而“无靶可打”。第二军医大学长征医院泌尿外科王林辉课题组与东方肝胆外科医院生物信号转导实验室主任王红阳院士研究组合作,发现了一条介导肾癌靶向药物耐药形成的新型长链非编码RNA——lncARSR (lncRNA Activated in RCC with Sunitinib Resistance),可作为预测靶向药物治疗疗效的分子标志物和逆转靶向药物耐药的干预靶点,使晚期肾癌患者接受更加精准化、个性化的治疗成为可能。5月11日,这一研究成果发表在国际权威学术期刊《肿瘤细胞》Cancer Cell上。

长链非编码RNA最初被认为是DNA转录过程中的一种“噪音”,不具有生物学功能。然而,近年来的研究表明其具有举足轻重的调节作用。联合研究团队将目光聚焦到长链非编码RNA,在肾癌组织和血浆中发现了一条新型的长链非编码RNA,并将其命名为lncARSR。研究发现,不同肾癌患者体内lncARSR含量不同,含量较低者的靶向药物舒尼替尼治疗效果较好,反之则疗效欠佳。据此,研究组提出将lncARSR作为预测肾癌患者舒尼替尼治疗疗效的组织学和血清学标志物。这种lncARSR可以通过外泌体进行传播,诱导更多的肿瘤细胞耐药。


进一步研究发现,lncARSR 诱导对Sunitinib 耐药主要通过竞争性结合miR-34/miR-449,以增强肾癌细胞中的AXL 和 c-MET 表达起到作用。通过使用lncARSR抑制物或靶向抑制AXL和c-MET小分子药物,能恢复耐药性肾癌对舒尼替尼的敏感性,可作为逆转肾癌舒尼替尼耐药的治疗新策略,并已经在动物实验中得到了印证。

原始出处:

Qu L, Ding J, Chen C, Wu ZJ, Liu B, Gao Y, Chen W, Liu F, Sun W, Li XF, Wang X, Wang Y, Xu ZY, Gao L, Yang Q, Xu B, Li YM, Fang ZY, Xu ZP, Bao Y, Wu DS, Miao X, Sun HY, Sun YH, Wang HY, Wang LH. Exosome-Transmitted lncARSR Promotes Sunitinib Resistance in Renal Cancer by Acting as a Competing Endogenous RNA. Cancer Cell. 2016 May 9;29(5):653-68

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    2016-08-20 维他命
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    2016-11-12 zhujh4277

    外泌体与肿瘤的关系值得深入研究研究

    0

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    2016-09-04 d830384
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    2016-09-30 1e10c84am36(暂无匿称)

    拜读,好文

    0

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    2016-05-18 yxch36
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