Abstract
BackgroundSUMO-activating enzyme subunit 2 (SAE2) is the sole E1-activating enzyme required for numerous important protein SUMOylation, abnormal of which is associated with carcinogenesis. SAE2 inactivation was recently reported to be a therapeutic strategy in cancers with Myc overexpression. However, the roles of SAE2 in small cell lung cancer (SCLC) are largely unknown.MethodsStably SAE2 knockdown in H446 cells were established with a lentiviral system. Cell viability, cell cycle, and apoptosis were analyzed using MTT assay and flow cytometric assay. Expression of SAE2 mRNA and protein were detected by qPCR, western blotting, and immunohistochemical staining. Cell invasion and migration assay were determined by transwell chamber assay. H446 cells with or without SAE2 knockdown, nude mice models were established to observe tumorigenesis.ResultsSAE2 was highly expressed in SCLC and significantly correlated with tumorigenesis in vivo. Cancer cells with RNAi-mediated reduction of SAE2 expression exhibited growth retardation and apoptosis increasing. Furthermore, down-regulation of SAE2 expression inhibited migration and invasion, simultaneously increased the sensitivity of H446 to etoposide and cisplatin.ConclusionsSAE2 plays an important role in tumor growth, metastasis, and chemotherapy sensitivity of H446 and is a potential clinical biomarker and therapeutic target in SCLC with high c-Myc expression.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-015-0164-y) contains supplementary material, which is available to authorized users.
Highlights
small ubiquitin modifier (SUMO)-activating enzyme subunit 2 (SAE2) is the sole E1-activating enzyme required for numerous important protein SUMOylation, abnormal of which is associated with carcinogenesis
The mRNA and protein level of SAE2 were detected using quantitative real-time PCR and Western blot in several cell lines, including H446, H526, H69, H146, and BEAS-2B. Both mRNA expression and protein levels of SAE2 were significantly higher in small cell lung cancer (SCLC) cell lines compared with normal cell line (BEAS-2B) (Fig. 1b, c).These results indicated that SAE2 is highly expressed in SCLC tissues and cell lines
Downregulation of SAE2 inhibited cell growth mainly by inducing cell apoptosis, we examined the apoptosis of SAE2 down-regulated cells treated with etoposide or cisplatin and showed that proportion of apoptotic cells was significantly increased in shSAE2-H446 cells (Fig. 6a, b)
Summary
SUMO-activating enzyme subunit 2 (SAE2) is the sole E1-activating enzyme required for numerous important protein SUMOylation, abnormal of which is associated with carcinogenesis. SAE2 inactivation was recently reported to be a therapeutic strategy in cancers with Myc overexpression. The roles of SAE2 in small cell lung cancer (SCLC) are largely unknown. Small cell lung cancer (SCLC) accounts for 13 % of all newly diagnosed cases of lung cancer worldwide, representing approximately 180,000 cases per year [3,4,5]. Patients at extensive stage have median survival of 7–12 months, and 5-year survival is only 1–2 %. Whereas among patients at limited stage, median survival is about. SCLC is the most aggressive type of lung cancer mainly due to rapid growth, wide invasion, and fast metastasis [8, 11,12,13]. It is critical to investigate an effective strategy for SCLC treatment
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