The prolyl hydroxylase OGFOD1 promotes cancer cell proliferation by regulating the expression of cell cycle regulators
The prolyl hydroxylase OGFOD1 promotes cancer cell proliferation by regulating the expression of cell cycle regulators
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DOI：
10.1002/1873-3468.14547
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发表时间：
2022-12
期刊：
影响因子：
3.5
通讯作者：
Toshiya Fujisaki;Ken Saito;T. Kikuchi;E. Kondo
中科院分区：
文献类型：
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作者：
Toshiya Fujisaki;Ken Saito;T. Kikuchi;E. Kondo
据报道，OGFOD1 是一种脯氨酰羟化酶，可响应细胞应激从细胞核转位至细胞质。在这里，我们证明 OGFOD1 调节细胞周期相关基因的转录和转录后稳定性。肺癌细胞中 OGFOD1 敲低通过特异性消耗细胞周期蛋白依赖性激酶 (CDK) 1、CDK2 和细胞周期蛋白 B1 (CCNB1) mRNA 以及 p21Cip1 的核积累来诱导细胞周期停滞。对这些细胞中 mRNA 动态的分析表明，CDK1 以时间依赖性方式减少，反映了 OGFOD1 和 RNA 结合蛋白 HuR 的转录后调节。相反，CDK2 和 CCNB1 的耗竭是由 OGFOD1 介导的转录减少引起的。这些结果表明，OGFOD1 是维持癌细胞增殖过程中特定细胞周期调节因子的功能所必需的。
OGFOD1, a prolyl‐hydroxylase, has been reported to translocate from the nucleus to the cytoplasm in response to cellular stress. Here, we demonstrate that OGFOD1 regulates the transcription and post‐transcriptional stabilization of cell cycle‐related genes. OGFOD1 knockdown in lung cancer cells induced cell cycle arrest through the specific depletion of cyclin‐dependent kinase (CDK) 1, CDK2 and cyclin B1 (CCNB1) mRNAs and the nuclear accumulation of p21Cip1. Analysis of the mRNA dynamics in these cells revealed that CDK1 decreased in a time‐dependent manner, reflecting post‐transcriptional regulation by OGFOD1 and the RNA‐binding protein HuR. In contrast, the depletion of CDK2 and CCNB1 resulted from decreased transcription mediated by OGFOD1. These results indicate that OGFOD1 is required to maintain the function of specific cell cycle regulators during cancer cell proliferation.