WITHDRAWN: Elevated glucose promotes DNA replication and cancer cell growth through pRB-E2F1.

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Abstract

The full text of this preprint has been withdrawn by the authors due to author disagreement with the posting of the preprint. Therefore, the authors do not wish this work to be cited as a reference. Questions should be directed to the corresponding author.

升高的葡萄糖通过pRB-E2F1促进DNA复制和癌症细胞生长。
尽管流行病学研究强调了高血糖与癌症风险增加之间的联系,但对这种联系背后的分子机制的了解仍然有限。在这项研究中,我们报道了高血糖水平(HG)增强DNA复制,导致肿瘤细胞生长。此外,通过全基因组分析,我们确定E2F1是HG诱导的细胞适应的核心转录因子。对E2F1的抑制消除了HG诱导的DNA合成和细胞生长,支持了E2F1在这一过程中的作用。此外,我们证明,升高的葡萄糖水平增强了pRB磷酸化,这在E2F1激活中起作用。有趣的是,在HG诱导的E2F1靶基因中,RRM2(核糖核苷酸还原酶调节亚基M2)通过催化DNA复制所必需的dNTP的产生参与核苷酸合成。我们发现HG以E2F1-RRM2依赖的方式增加细胞dNTP水平,这与增强的DNA合成和癌症细胞生长相关。总之,我们的发现揭示了高血糖与癌症细胞增殖之间的pRB-E2F1-RRM2依赖性联系,并提供了高血糖引导肿瘤细胞进行DNA复制的分子机制。
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