Our recent studies have shown that haspin, a protein kinase imperative for mitosis, is engaged in the interphase progression of HeLa and U2OS cancer cells. In this investigation, we employed the Fucci reporter system and time-lapse imaging to examine the impact of haspin gene silencing on cell cycle progressions at a single-cell level. We found that the loss of haspin induced multiple cell cycle defects. Specifically, the S/G2 duration was greatly prolonged by haspin gene depletion or inhibition in synchronous HeLa cells. Haspin gene depletion in asynchronous HeLa and U2OS cells led to a similarly protracted S/G2 phase, followed by mitotic cell death or postmitotic G1 arrest. In addition, haspin deficiency resulted in robust induction of the p21^CIP1/WAF1 checkpoint protein, a target of the p53 activation. Also, co-depleting haspin with either p21 or p53 could rescue U2OS cells from postmitotic G1 arrest and partially restore their proliferation. These results substantiate the haspin's capacity to regulate interphase and mitotic progression, offering a broader antiproliferative potential of haspin loss in cancer cells.

中文翻译：

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haspin 的缺失通过在多个阶段干扰细胞周期进程来抑制癌细胞增殖

我们最近的研究表明，haspin，一种对有丝分裂必不可少的蛋白激酶，参与了 HeLa 和 U2OS 癌细胞的间期进展。在这项调查中，我们采用 Fucci 报告系统和延时成像来检查 haspin 基因沉默对单细胞水平的细胞周期进程的影响。我们发现 haspin 的缺失会导致多个细胞周期缺陷。具体而言，同步 HeLa 细胞中的 haspin 基因消耗或抑制大大延长了 S/G2 持续时间。异步 HeLa 和 U2OS 细胞中的 Haspin 基因耗竭导致类似延长的 S/G2 期，随后是有丝分裂细胞死亡或有丝分裂后 G1 期停滞。此外，haspin 缺乏导致 p21 ^{CIP1/WAF1 的}强烈诱导检查点蛋白，p53 激活的目标。此外，与 p21 或 p53 共同消耗 haspin 可以从有丝分裂后的 G1 期停滞中拯救 U2OS 细胞并部分恢复它们的增殖。这些结果证实了 haspin 调节间期和有丝分裂进展的能力，为癌细胞中的 haspin 损失提供了更广泛的抗增殖潜力。