Chen G M, Ding R F, Tan Y D, Pan X B, Jiang G M, He J F, Lin S H, Liu C, Jia Y
Surgical Department, Dongguan People's Hospital, Dongguan City, China.
Department of Medical Oncology, Dongguan People's Hospital, Dongguan City, China.
Genet Mol Res. 2015 Apr 27;14(2):4005-14. doi: 10.4238/2015.April.27.15.
Casein kinase 2 interacting protein 1 (CKIP1) is a specific interacting protein of the casein kinase 2 (CK2) α subunit, and, by binding CK2 and other proteins, functions as an adaptor to regulate a series of cellular functions. Previous studies suggested that CKIP1 might play an important role in regulating oncogenic activities. However, few studies examining the function of CKIP1 in cancer cells have been performed. The present study aimed to investigate the role of CKIP1 in lung cancer. CKIP1 mRNA expression was detected in 5 human lung cancer cell lines (H-125, H1299, LTEP-A-2, SPC-A-1, and NCL-H446) by semi-quantitative RT-PCR, and in 10 noncancerous lung tissues and 30 non-small lung cancer tissues by real-time quantitative PCR. A lentivirus-mediated small interfering RNA (siRNA) was used to knock down CKIP1 expression in the H1299 cell line. To elucidate the impact of CKIP1 downregulation on H1299 cells, cell proliferation, DNA synthesis, and cell cycle distribution and apoptosis were measured by high content screening assay, BrdU incorporation, and flow cytometric analyses, respectively. CKIP1 mRNA was highly expressed both in H1299 cells and lung cancer tissues. We found that downregulation of CKIP1 resulted in suppression of proliferation and colony-forming ability of H1299 cells, and led to S phase cell cycle arrest and G2 phase promotion, as well as a significant enhancement of H1299 cell apoptosis. Our study indicated that high expression levels of CKIP1 were associated with the development of lung cancer, and that CKIP1 knockdown may block tumor cell growth mainly by promoting cell apoptosis.
酪蛋白激酶2相互作用蛋白1（CKIP1）是酪蛋白激酶2（CK2）α亚基的特异性相互作用蛋白，通过结合CK2和其他蛋白质，作为衔接蛋白发挥作用，调节一系列细胞功能。先前的研究表明，CKIP1可能在调节致癌活性中发挥重要作用。然而，很少有研究检测CKIP1在癌细胞中的功能。本研究旨在探讨CKIP1在肺癌中的作用。通过半定量RT-PCR在5种人肺癌细胞系（H-125、H1299、LTEP-A-2、SPC-A-1和NCL-H446）中检测CKIP1 mRNA表达，并通过实时定量PCR在10个非癌性肺组织和30个非小细胞肺癌组织中检测。使用慢病毒介导的小干扰RNA（siRNA）敲低H1299细胞系中的CKIP1表达。为了阐明CKIP1下调对H1299细胞的影响，分别通过高内涵筛选分析、BrdU掺入和流式细胞术分析测量细胞增殖、DNA合成、细胞周期分布和细胞凋亡。CKIP1 mRNA在H1299细胞和肺癌组织中均高表达。我们发现，CKIP1的下调导致H1299细胞的增殖和集落形成能力受到抑制，并导致S期细胞周期停滞和G2期进展，以及H1299细胞凋亡的显著增强。我们的研究表明，CKIP1的高表达水平与肺癌的发生发展相关，并且敲低CKIP1可能主要通过促进细胞凋亡来阻断肿瘤细胞生长。
