Overexpression and biological function of TMEM48 in non-small cell lung carcinoma

被引:39
作者
Qiao, Wenliang [1 ]
Han, Yudong [1 ]
Jin, Wei [2 ]
Tian, Mi [3 ]
Chen, Pei [1 ]
Min, Jie [4 ]
Hu, Haiyang [1 ]
Xu, Binbin [1 ]
Zhu, Wenzhuo [1 ]
Xiong, Liwen [5 ]
Lin, Qiang [1 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 1, Dept Thorac Surg, 100 Haining Rd, Shanghai 200080, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Med, Key Lab Cell Differentiat & Apoptosis, Chinese Minist Educ, Shanghai 200030, Peoples R China
[3] Shanghai Jiao Tong Univ, Sch Med, State Key Lab Oncogenes & Related Genes, Shanghai Canc Inst,Renji Hosp, Shanghai 200030, Peoples R China
[4] Second Mil Med Univ, Dept Cardiothorac Surg, Shanghai Changzheng Hosp, Shanghai, Peoples R China
[5] Shanghai Jiao Tong Univ, Dept Pulm Med, Shanghai Chest Hosp, 241 West Huaihai Rd, Shanghai 200030, Peoples R China
基金
中国国家自然科学基金;
关键词
TMEM48; NSCLC; Proliferation; Cell cycle; Metastasis; NUCLEAR-PORE COMPLEX; DNA-REPLICATION; CANCER; CYCLE; NUCLEOPORIN; TRANSPORT; INVASION; NDC1;
D O I
10.1007/s13277-015-4014-x
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Transmembrane protein 48 (TMEM48), localized to nuclear pore complexes (NPCs), has been reported crucial for NPC assembly. Alterations in NPC members have been reported in several malignancies. The present study was aimed to elucidate the expression and biological function of TMEM48 in non-small cell lung carcinoma (NSCLC). Here, TMEM48 expression level was higher in NSCLC tissues than that in the adjacent normal tissues. Moreover, higher TMEM48 expression was correlated with a more advanced tumor stage, lymph node metastasis, bigger tumor size tumor stage, and shorter survival time. Knockdown of TMEM48 in NSCLC cell lines, A549 and H1299, inhibited cell proliferation and significantly increased cells population in G1 phase. Gene set enrichment analysis (GSEA) showed that cell cycle pathway was correlative with the TMEM48 expression. Additionally, real-time PCR and western blot analysis revealed that several cell cycle and DNA replication genes, including Cyclin B1, CDK1, CDC6, PCNA, and RCF4, were reduced after TMEM48 knockdown. Additionally, inhibition of TMEM48 in NSCLC cells significantly stimulated cell apoptosis, while notably repressed cell adhesion, migration, invasion, and tumorigenicity in nude mice. Our data provide insight into the biological relevance of TMEM48 in NSCLC progression and highlight its usefulness as a prognostic factor and potential therapeutic target in NSCLC.
引用
收藏
页码:2575 / 2586
页数:12
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