Xie Xiao, Xiao Haibo, Ding Fangbao, Zhong Hong, Zhu Jiaquan, Ma Nan, Mei Ju
Xin Hua Hospital Affiliated with the Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
Xin Hua Hospital Affiliated with the Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
Cancer Genet. 2014 May;207(5):188-94. doi: 10.1016/j.cancergen.2014.04.008. Epub 2014 May 4.
Prolyl hydroxylase-1 (PHD1), a member of the hypoxia inducible factor (HIF)-PHD family, plays an important role in regulating the stability of HIFs. The nuclear factor-κB (NF-κB) pathway consists of a family of transcription factors that play critical roles in inflammation, immunity, cell proliferation, differentiation, and survival. In this study, we demonstrate that PHD1 can inhibit NF-κB activity and its target genes in lung cancer cells based on both over-expression and RNA interference-mediated knockdown of PHD1 in human A549 lung cancer cells and HEK293 T cells. Of medical importance, PHD1 could induce cell cycle arrest in lung cancer cells, resulting in the suppression of cell proliferation. Xenograft tumor growth assays indicate that PHD1 plays a critical role in suppressing lung cancer growth. These findings reveal a new role of PHD1 in lung cancer and provide new treatment perspectives for cancer therapy by characterizing PHD1 as a potential target.
脯氨酰羟化酶-1（PHD1）是缺氧诱导因子（HIF）-PHD家族的成员之一，在调节HIF的稳定性方面发挥着重要作用。核因子-κB（NF-κB）信号通路由一族转录因子组成，这些转录因子在炎症、免疫、细胞增殖、分化和存活中起着关键作用。在本研究中，我们通过在人A549肺癌细胞和HEK293 T细胞中过表达和RNA干扰介导的PHD1敲低，证明了PHD1可以抑制肺癌细胞中的NF-κB活性及其靶基因。具有医学重要性的是，PHD1可诱导肺癌细胞的细胞周期停滞，从而抑制细胞增殖。异种移植肿瘤生长试验表明，PHD1在抑制肺癌生长中起关键作用。这些发现揭示了PHD1在肺癌中的新作用，并通过将PHD1鉴定为潜在靶点为癌症治疗提供了新的治疗前景。
