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Mol Cell:长片段非编码RNA促进肿瘤生长机制

2013-12-25 佚名 《分子细胞》

从中国科学技术大学获悉,该校生命科学学院吴缅和梅一德教授研究组,揭示了长片段非编码RNA通过调控肿瘤细胞瓦伯格效应促进肿瘤生长的机制。相关研究近日在线发表在国际著名学术期刊《细胞》子刊《分子细胞》。 肿瘤细胞即使在有氧状态下也优先进行糖酵解,而不是通过产能效率更高的氧化磷酸化途径为细胞生长提供能量,这就是瓦伯格效应。低氧微环境下,肿瘤细胞也能促进瓦伯格效应,但具体的分

从中国科学技术大学获悉,该校生命科学学院吴缅和梅一德教授研究组,揭示了长片段非编码RNA通过调控肿瘤细胞瓦伯格效应促进肿瘤生长的机制。相关研究近日在线发表在国际著名学术期刊《细胞》子刊《分子细胞》。 【原文下载】

肿瘤细胞即使在有氧状态下也优先进行糖酵解,而不是通过产能效率更高的氧化磷酸化途径为细胞生长提供能量,这就是瓦伯格效应。低氧微环境下,肿瘤细胞也能促进瓦伯格效应,但具体的分子机制目前还不明确,特别是长片段非编码RNA是否也参与调控低氧环境下肿瘤的瓦伯格效应迄今没有报道。

长片段非编码RNA是指长度大于200个核苷酸的RNA分子。吴缅研究组发现,一个叫lincRNA-p21的长片段非编码RNA分子可以被低氧诱导因子HIF-1α(一种重要的调控肿瘤细胞发生发展的蛋白分子)诱导表达。正常情况下,HIF-1α和蛋白分子VHL结合,并被后者降解,使HIF-1α在肿瘤细胞中的表达水平不至于太高,从而抑制肿瘤的过快生长和转移。但在低氧情况下,被诱导表达的lincRNA-p21分子通过分别结合HIF-1α和VHL,来阻止HIF-1α-VHL复合物的形成,导致HIF-1α蛋白水平提高,最终形成一个正反馈循环,促进瓦伯格效应,使肿瘤发生恶变。


他们通过小鼠实验证明了这一观点,表明lincRNA-p21作为一个癌基因,在体内发挥功能。这一研究结果首次阐明了长片段非编码RNA在调控肿瘤细胞瓦伯格效应中的重要作用,也说明lincRNA-p21可以作为肿瘤治疗的潜在靶点。

原文出处:

Yang F, Zhang H, Mei Y, Wu M.Reciprocal Regulation of HIF-1α and LincRNA-p21 Modulates the Warburg Effect.Mol Cell. 2013 Dec 3. pii: S1097-2765(13)00829-0. doi: 10.1016/j.molcel.2013.11.004. 【原文下载】

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    2014-03-11 d830384
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    2014-03-06 维他命
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