Alteration in gene expression profile and biological behavior in human lung cancer cell line NL9980 by nm23-H1 gene silencing

Wei Ma, Jun Chen, Xingyang Xue, Zhuomin Wang, Hongyu Liu, Ting Wang, Yun Bai, Shou-Ching Tang, Qinghua Zhou

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Lung cancer is the leading cause of cancer death in both men and women. Tumor metastasis is an essential aspect of lung cancer progression. nm23-H1 is a metastasis suppressor gene. The molecular mechanism by which nm23-H1 suppresses the metastasis is still unclear. Here, we compared the gene expression profile of human large cell lung cancer cell line NL9980 by nm23-H1 gene silencing with that of negative control cells to comprehensively investigate nm23-H1-mediated changes in gene expression of NL9980 cells. Microarray assay revealed that expression of 733-known genes (1.9%, 733/38,500) were altered in response to nm23-H1 gene silencing, including 466 upregulated genes and 267 downregulated. real-time PCR assay of the expression changes indicated that 81.82% (45/55) of verified genes were consistent with that observed in microarray assay. The upregulated genes included MMP-1, -2, SNAI2, CXCL1, 2, 3, PAI-2, while the downregulated genes included cystatin B, TIMP-2, E-cadherin, centrin-2, all of which have been associated with tumor metastasis. Furthermore, we confirmed by Western blot that the expression of MMP-1 and -2 were significantly increased while that of cystatin B was dramatically decreased in NL9980-nm23-H1 silencing cells. The NL9980-nm23-H1 silencing cells exhibited significantly more S phase growth and invasive ability. Thus, silencing of nm23-H1 gene caused metastasis-related gene expression changes in lung cancer cells. The knockdown of nm23-H1 expression may change the lung cancer cells to a more invasive phenotype through alteration in the expression of a set of genes.

Original languageEnglish (US)
Pages (from-to)425-430
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume371
Issue number3
DOIs
StatePublished - Jul 4 2008

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Keywords

  • Lung cancer
  • Metastasis suppressor gene
  • NL9980 cell line
  • nm23-H1

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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