Lentivirus-mediated knockdown of NLK inhibits small-cell lung cancer growth and metastasis.
Lentivirus-mediated knockdown of NLK inhibits small-cell lung cancer growth and metastasis.
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慢病毒介导的NLK敲低抑制小细胞肺癌的生长和转移
DOI：
10.2147/dddt.s87435
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Jiang S
中科院分区：
文献类型：
--
作者：
Lv M;Li Y;Tian X;Dai S;Sun J;Jin G;Jiang S
Nemo-like kinase（NLK）是一种进化上保守的丝氨酸/苏氨酸激酶，被认为是多种癌症的关键调节因子。在这项研究中，我们研究了NLK在人类小细胞肺癌（SCLC）中的作用，SCLC是最具侵袭性的肺癌。在20对新鲜SCLC组织样本中通过定量实时聚合酶链反应评价NLK表达，发现在肿瘤组织中显著升高。慢病毒介导的RNAi有效抑制NCI-H446细胞中的NLK表达，导致体外细胞活力和增殖显著降低。此外，NLK的敲低通过抑制细胞周期蛋白A、CDK 2和CDC 25 A导致细胞周期停滞在S期，这可能有助于细胞生长抑制。此外，敲低NLK降低NCI-H446细胞的迁移，下调基质金属蛋白酶9。用NLK短发夹RNA治疗显著降低体内SCLC肿瘤生长。总之，本研究表明，NLK在小细胞肺癌的生长和转移中起重要作用，并可能作为治疗小细胞肺癌的潜在治疗靶点。
Nemo-like kinase (NLK), an evolutionarily conserved serine/threonine kinase, has been recognized as a critical regulator of various cancers. In this study, we investigated the role of NLK in human small-cell lung cancer (SCLC), which is the most aggressive form of lung cancer. NLK expression was evaluated by quantitative real-time polymerase chain reaction in 20 paired fresh SCLC tissue samples and found to be noticeably elevated in tumor tissues. Lentivirus-mediated RNAi efficiently suppressed NLK expression in NCI-H446 cells, resulting in a significant reduction in cell viability and proliferation in vitro. Moreover, knockdown of NLK led to cell cycle arrest at the S-phase via suppression of Cyclin A, CDK2, and CDC25A, which could contribute to cell growth inhibition. Furthermore, knockdown of NLK decreased the migration of NCI-H446 cells and downregulated matrix metalloproteinase 9. Treatment with NLK short hairpin RNA significantly reduced SCLC tumor growth in vivo. In conclusion, this study suggests that NLK plays an important role in the growth and metastasis of SCLC and may serve as a potential therapeutic target for the treatment of SCLC.