Overexpression of ZIC5 promotes proliferation in non-small cell lung cancer.
BACKGROUND
Non-small cell lung cancer (NSCLC) has become the leading cause of cancer-related deaths. It is therefore urgent that we identify new molecular targets to help cure NSCLC patients. Here, we identified ZIC5 as a potential novel oncogene.


METHODS
We detected the expression of ZIC5 in tumor and normal tissues of NSCLC patients using quantitative real-time PCR and explored its clinical appearance. We then knocked down ZIC5 to observe changes in NSCLC cell proliferation and metastasis. Nude mouse xenograft models were established to measure ZIC5's function in vivo.


RESULTS
Our results revealed that ZIC5 was expressed at dramatically higher levels in NSCLC tumor tissues than in normal tissues. High levels of ZIC5 expression were associated with a higher primary tumor grade. ZIC5 expression was significantly inhibited by small interfering RNA. After silencing ZIC5, the metastatic capacity of NSCLC cells was clearly lower. Knocking down ZIC5 significantly inhibited the proliferation of NSCLC cells, causing the cell cycle to be arrested in G2 phase. Xenograft tumor models showed that knocking down ZIC5 also inhibited tumor growth in vivo. Q-PCR and western blot analysis revealed that ZIC5 expression was closely associated with CCNB1 and CDK1 complex expression, while other cell cycle-related genes showed no significant correlation with ZIC5.


CONCLUSIONS
Our experiment show that ZIC5 is highly upregulated in NSCLC tumor tissues and suggest that ZIC5 may act as an oncogene by influencing CCNB1 and CDK1 complex expression. ZIC5 may therefore be a potential biomarker and therapeutic target for NSCLC patients.
Department of Cardiothoracic Surgery, Jinling Hospital, Southern Medical University, East Zhongshan Road 305, Xuanwu District, Nanjing, Jiangsu 210002, PR China. Electronic address: sunqi129@gmail.com.
Qi
Q
Sun
Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Baiziting 42, Xuanwu District, Nanjing, 210009, PR China. Electronic address: shirun@outlook.com.
Run
R
Shi
Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Baiziting 42, Xuanwu District, Nanjing, 210009, PR China. Electronic address: wangxin00320@hotmail.com.
Xin
X
Wang
Department of Cardiothoracic Surgery, Jinling Hospital, Southern Medical University, East Zhongshan Road 305, Xuanwu District, Nanjing, Jiangsu 210002, PR China. Electronic address: dr.deminli@gmail.com.
Demin
D
Li
Department of Cardiothoracic Surgery, Jinling Hospital, Clinical Medicine School of Nanjing University, East Zhongshan Road 305, Xuanwu District, Nanjing, Jiangsu 210002, PR China. Electronic address: wu_hai_wei@163.com.
Haiwei
H
Wu
Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Baiziting 42, Xuanwu District, Nanjing, 210009, PR China. Electronic address: ren_bin_hui@163.com.
Binhui
B
Ren
D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D016203:CDC2 Protein Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D056744:Cyclin B1 / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism*
D014408:Biomarkers, Tumor; C534699:CCNB1 protein, human; D056744:Cyclin B1; D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; C485965:ZIC5 protein, human; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases
CCNB1; CDK1; NSCLC; Oncogene; Proliferation; ZIC5