title: Lentivirus-mediated knockdown of NLK inhibits small-cell lung cancer growth and metastasis.
abstract: 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.
authors.affiliation: Department of Nuclear Medicine.
authors.forename: Mutian
authors.initials: M
authors.lastname: Lv
authors.affiliation: Department of Nuclear Medicine.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Li
authors.affiliation: Molecular Oncology Laboratory of Cancer Research Institute, The First Affiliated Hospital of China Medical University.
authors.forename: Xin
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Pathology, The First Affiliated Hospital, College of Basic Medical Sciences of China Medical University; Department of Pathology, Institute of Pathology and Pathophysiology.
authors.forename: Shundong
authors.initials: S
authors.lastname: Dai
authors.affiliation: Department of Immunology and Biotherapy, Liaoning Cancer Hospital and Institute.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Laboratory Medicine.
authors.forename: Guojiang
authors.initials: G
authors.lastname: Jin
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Shenyi
authors.initials: S
authors.lastname: Jiang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D016086:Lentivirus; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D034622:RNA Interference; D011817:Rabbits; D055752:Small Cell Lung Carcinoma / Q000201:enzymology* / Q000473:pathology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C470551:NLK protein, human; D017346:Protein Serine-Threonine Kinases
keywords: NLK; RNAi; SCLC; migration; proliferation