title: Knockdown of SUMO-activating enzyme subunit 2 (SAE2) suppresses cancer malignancy and enhances chemotherapy sensitivity in small cell lung cancer.
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.
authors.affiliation: Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China. liuxk57@163.com.
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Thoracic Oncology, Cancer Center , West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China. xy868996@163.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China. pzgxy@sohu.com.
authors.forename: Zongguo
authors.initials: Z
authors.lastname: Pang
authors.affiliation: Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China. gfcdyx2008@163.com.
authors.forename: Fuchun
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China. qinqingscu@126.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: Qin
authors.affiliation: Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China. yintao03073@163.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Yin
authors.affiliation: Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China. yaxiongsang@gmail.com.
authors.forename: Yaxiong
authors.initials: Y
authors.lastname: Sang
authors.affiliation: Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China. leymj@163.com.
authors.forename: Chengjun
authors.initials: C
authors.lastname: Feng
authors.affiliation: Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China. lixiaoyu2012huaxi@163.com.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China. summer.jl06@foxmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China. keyanxiaozhu@163.com.
authors.forename: Pei
authors.initials: P
authors.lastname: Shu
authors.affiliation: Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China. wangys@scu.edu.cn.
authors.forename: Yongsheng
authors.initials: Y
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mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics*; D051379:Mice; D055752:Small Cell Lung Carcinoma / Q000235:genetics*