title: Regulation of SIRT2 levels for human non-small cell lung cancer therapy.
abstract: Seven Sirtuin family members (SIRT1-7), comprising a family of NAD+-dependent protein deacetylases and ADP-ribosyltransferases, are key proteins that regulate multiple physiological processes. SIRT2 was recently reported to play an important role in carcinogenesis. However, its role in non-small cell lung cancer (NSCLC) has not yet been investigated. In this study, we analyzed the expression pattern of SIRT2 in NSCLC tissues from clinical patients and in cell lines, and found that SIRT2 was significantly down-regulated at both the mRNA and protein levels in tumor than non-tumor tissues or cells, which were corroborated by the NSCLC tissue microarray results. Overexpression of SIRT2 in A549 and H1299 cells caused cell proliferation inhibition, cell apoptosis induction and cell cycle arrest. Further analysis showed that SIRT2 overexpression increased the ROS (reactive oxygen species) production and p27 levels. Moreover, up-regulation of SIRT2 in NSCLC cells increased the sensitivity to Cisplatin treatment. Taken together, our results implied that down-regulation of SIRT2 was associated with NSCLC, and regulation of SIRT2 might be an important target for NSCLC therapy.
authors.affiliation: Shanghai Lung Cancer Center, Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200030, People's Republic of China.
authors.forename: Ziming
authors.initials: Z
authors.lastname: Li
authors.forename: Qian Reuben
authors.initials: QR
authors.lastname: Xie
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Chen
authors.forename: Shun
authors.initials: S
authors.lastname: Lu
authors.forename: Weiliang
authors.initials: W
authors.lastname: Xia
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D056564:Sirtuin 1 / Q000378:metabolism; D056565:Sirtuin 2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C447939:SIRT1 protein, human; C474199:SIRT2 protein, human; D056564:Sirtuin 1; D056565:Sirtuin 2; D002945:Cisplatin
keywords: Cancer therapy; NSCLC; Non-small cell lung cancer; ROS; SIRT; SIRT2; non-small lung cancer; reactive oxygen species; sirtuin