A novel PHD-finger protein 14/KIF4A complex overexpressed in lung cancer is involved in cell mitosis regulation and tumorigenesis

A novel PHD-finger protein 14/KIF4A complex overexpressed in lung cancer is involved in cell mitosis regulation and tumorigenesis
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肺癌中过表达的新型 PHD-finger 蛋白 14/KIF4A 复合物参与细胞有丝分裂调节和肿瘤发生

DOI:
10.18632/oncotarget.14962
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发表时间:
2017-02
期刊:
影响因子:
--
通讯作者:
Zhang Z.
Zhang Z.
中科院分区:
--
文献类型:
--
作者:
Zhang L;Huang Q;Lou J;Zou L;Wang Y;Zhang P;Yang G;Zhang J;Yu L;Yan D;Zhang C;Qiao J;Wang S;Wang S;Xu Y;Ji H;Chen Z;Zhang Z.

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含有植物同源结构域(PHD)指的蛋白质与包括癌症在内的许多人类疾病有关。在这项研究中,我们发现PHF 14,一个新发现的PHD指蛋白,在肺癌中高表达。PHF 14的高表达水平与肺癌患者的腺癌和低生存率相关。敲低PHF14抑制癌细胞生长和癌变,而过表达PHF14促进细胞增殖。在细胞分裂过程中,PHF14直接结合并与KIF4A(一种参与肺癌发生的核动力蛋白)共定位,形成功能复合物。与KIF4A耗竭的作用类似,在几种细胞系中沉默PHF14导致细胞有丝分裂缺陷,M期延长,并抑制细胞增殖。此外,这两种蛋白对细胞增殖具有协同作用,并且在肺癌组织中显著共过表达。我们的数据为PHD指蛋白的生物学意义提供了新的见解,并暗示PHF14可能是肺癌的潜在生物标志物。
The plant homeodomain (PHD) finger-containing proteins have been implicated in many human diseases including cancer. In this study, we found that PHF14, a newly identified PHD finger protein, is highly expressed in lung cancer. The high expression level of PHF14 was associated with adenocarcinoma and poor survival in lung cancer patients. Knocking down PHF14 suppressed cancer cell growth and carcinogenesis, while over-expressing PHF14 promoted cell proliferation. During cell division, PHF14 directly bound to and co-localized with KIF4A (a nuclear motor protein involved in lung carcinogenesis) to form a functional complex. Similarly to the effect of KIF4A depletion, silencing PHF14 in several cell lines caused cell mitotic defects, prolonged M phase, and inhibited cell proliferation. What's more, these two proteins had a synergistic effect on cell proliferation and were significantly co-overexpressed in lung cancer tissues. Our data provide new insights into the biological significance of PHD finger proteins and imply that PHF14 may be a potential biomarker for lung cancer.
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