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

International Journal of Clinical and Experimental Pathology

Lin Han¹  Shi-Min Bao¹  Zhi-Qiang Yan¹  Li-Xin Chen¹  Xiao-Hua Liang¹ 

关键词: Non-small cell lung cancer;    brain metastasis;    RNAi screening;    epigenetics;    SIRT1;   

DOI  :  

学科分类：生理学与病理学

来源: e-Century Publishing Corporation

【 摘 要 】

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.

【 授权许可】

Unknown