Ploidy-dependent change in cyclin D2 expression and sensitization to cdk4/6 inhibition in human somatic haploid cells.
Ploidy-dependent change in cyclin D2 expression and sensitization to cdk4/6 inhibition in human somatic haploid cells.
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DOI：
10.1016/j.bbrc.2018.08.160
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发表时间：
2018-09
影响因子：
3.1
通讯作者：
Kan Yaguchi;Takahiro Yamamoto;Masaya Shimada;Rina Sugimoto;Kiminori Nakamura;T. Ayabe;Ryota Uehara-Ryota-Uehar
中科院分区：
文献类型：
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作者：
Kan Yaguchi;Takahiro Yamamoto;Masaya Shimada;Rina Sugimoto;Kiminori Nakamura;T. Ayabe;Ryota Uehara-Ryota-Uehar
在某些癌症类型中观察到近单倍体，但单倍体状态下基因调节的倍性依赖性改变仍然难以捉摸。通过对人类等基因单倍体和二倍体细胞系的转录组比较分析，我们发现单倍体细胞周期蛋白D2水平降低。单倍体的急性基因组复制使细胞周期蛋白D2的表达恢复到二倍体水平，表明细胞周期蛋白D2的表达调控与倍性直接相关。cyclin D2的下游通路，如Rb磷酸化和p27的隔离在单倍体中保持完整，这表明它们适应了cyclin D水平的降低。然而，有趣的是，与二倍体细胞相比，单倍体细胞更容易受到cdk4/6抑制。本研究结果表明，基于倍体连锁基因调控的单倍体细胞选择性生长抑制是可行的。
Near-haploidy is observed in certain cancer types, but ploidy-dependent alterations in gene regulation in the haploid state remain elusive. Here, by comparative transcriptome analysis between human isogenic haploid and diploid cell lines, we found lowering of cyclin D2 level in haploids. Acute genome duplication in haploids restored cyclin D2 expression to diploid level, indicating that the regulation of cyclin D2 expression is directly linked to ploidy. Downstream pathways of cyclin D2, such as Rb phosphorylation and p27 sequestration remained intact in haploids, suggesting that they adapt to lowered cyclin D level. Interestingly, however, haploid cells were more susceptible to cdk4/6 inhibition compared to diploids. Our finding indicates feasibility of selective growth suppression of haploid cells based on ploidy-linked gene regulation.