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Int J Clin Exp Pathol 2013;6(11):2357-2365

Original Article
SIRT1 is highly expressed in brain metastasis tissues of non-small cell lung cancer
(NSCLC) and in positive regulation of NSCLC cell migration

Lin Han, Xiao-Hua Liang, Li-Xin Chen, Shi-Min Bao, Zhi-Qiang Yan

The Experimental Animal Center, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; Department of
Oncology, Huashan Hospital, Fudan University, Shanghai, China. Equal contributors.

Received September 3, 2013; Accepted October 12, 2013; Epub October 15, 2013; Published November 1, 2013

Abstract: Brain metastases are a frequent and ongoing major complication of non-small cell lung cancer (NSCLC). To deepen our
understanding to the underlying mechanisms by which NSCLC cells metastasize to brain and hence to improve the therapy, a high throughput
RNAi screening with shRNA library of 153 epigenetic genes was subjected to A549, a NSCLC cell line with high migration ability, to examine
the effects of these genes on cell migration by wound-healing assay. The screening results showed that knockdown of 2 genes (KDM5B and
SIRT1) dramatically and specifically inhibits A549 migration but not affects the proliferation, which was subsequently confirmed through
transwell migration assay. Furthermore, SIRT1 is found to be highly expressed in brain metastasis tissues of NSCLC, compared to the NSCLC
tissues, suggesting that SIRT1 may play roles in brain metastasis of NSCLC. The relationship between SIRT1 expression and cell migration
ability was further investigated in three NSCLC cell lines and the result indicated that SIRT1 expression is tightly correlated with cell migration
ability. Collectively, our work provides potential biomarker and therapeutic target for brain metastasis of NSCLC. (IJCEP1309013).

Keywords: Non-small cell lung cancer, brain metastasis, RNAi screening, epigenetics, SIRT1

Address correspondence to: Zhi-Qiang Yan, The Experimental Animal Center, Shanghai Institute for Biological Sciences, Chinese Academy of
Sciences, Shanghai, China. E-mail: zqyan@sibs.ac.cn