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Published in: Journal of Hematology & Oncology 1/2015

Open Access 01-12-2015 | Research Article

Knockdown of SUMO-activating enzyme subunit 2 (SAE2) suppresses cancer malignancy and enhances chemotherapy sensitivity in small cell lung cancer

Authors: Xiaoke Liu, Yong Xu, Zongguo Pang, Fuchun Guo, Qing Qin, Tao Yin, Yaxiong Sang, Chengjun Feng, Xiaoyu Li, Li Jiang, Pei Shu, Yongsheng Wang

Published in: Journal of Hematology & Oncology | Issue 1/2015

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Abstract

Background

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. However, the roles of SAE2 in small cell lung cancer (SCLC) are largely unknown.

Methods

Stably 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.

Results

SAE2 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.

Conclusions

SAE2 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.
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Metadata
Title
Knockdown of SUMO-activating enzyme subunit 2 (SAE2) suppresses cancer malignancy and enhances chemotherapy sensitivity in small cell lung cancer
Authors
Xiaoke Liu
Yong Xu
Zongguo Pang
Fuchun Guo
Qing Qin
Tao Yin
Yaxiong Sang
Chengjun Feng
Xiaoyu Li
Li Jiang
Pei Shu
Yongsheng Wang
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2015
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-015-0164-y

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