title: Enhanced expression of cohesin loading factor NIPBL confers poor prognosis and chemotherapy resistance in non-small cell lung cancer.
abstract: BACKGROUND
  NIPBL, the sister chromatid cohesion 2 (SCC2) human homolog, is a cohesin loading factor which is essential for deposition of cohesin onto the sister chromatid. Recent studies have shown that NIPBL contribute to sister chromatid cohesion and plays a critical role in development, DNA repair, and gene regulation. In this study, we measured the expression of NIPBL in clinical non-small cell lung cancer specimens, and determined its effects on cellular processes and chemosensitivity in vitro.
  
  
  METHODS
  NIPBL immunohistochemistry was performed on 123 lung adenocarcinoma samples. Through knockdown of NIPBL protein expression, non-small cell lung cancer cell lines were used to test the potential involvement of NIPBL silencing on cell proliferation, migration, invasion, and apoptosis. Chemosensitivity was assessed with clonogenic assays, and chromatin immunoprecipitation assays were performed to analyze the relationship between NIPBL and signal transducers and activators of transcription 3 (STAT3).
  
  
  RESULTS
  Immunohistochemical analysis showed that high expression of NIPBL was strongly correlated with poor prognosis, tumor differentiation, and lymph node metastasis. Survival analysis further indicated that NIPBL expression was a potential prognostic factor for non-small cell lung cancer. Knockdown of NIPBL in non-small cell lung cancer cell lines significantly reduced cellular proliferation, migration, and invasion, and enhanced cellular apoptosis and sensitivity to cisplatin, paclitaxel, and gemcitabine hydrochloride. NIPBL bound to the promoter region of the STAT3 gene, directly regulating the expression of STAT3.
  
  
  CONCLUSIONS
  These data suggested that NIPBL played a significant role in lung carcinogenesis. NIPBL expression conferred poor prognosis and resistance to chemotherapy in non-small cell lung cancer, suggesting that NIPBL may be a novel therapeutic target.
authors.affiliation: Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), 38, Guangji Load, Hangzhou, Zhejiang, 310022, China. xwztjf@zju.edu.cn.|Cancer Research Institute, Zhejiang Cancer Hospital, 38, Guangji Load, Hangzhou, Zhejiang, 310022, China. xwztjf@zju.edu.cn.
authors.forename: Weizhen
authors.initials: W
authors.lastname: Xu
authors.affiliation: Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), 38, Guangji Load, Hangzhou, Zhejiang, 310022, China. yyy.1988.good@163.com.
authors.forename: Yinyin
authors.initials: Y
authors.lastname: Ying
authors.affiliation: Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), 38, Guangji Load, Hangzhou, Zhejiang, 310022, China. slhjiayou2010@163.com.
authors.forename: Lihong
authors.initials: L
authors.lastname: Shan
authors.affiliation: Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), 38, Guangji Load, Hangzhou, Zhejiang, 310022, China. fengjg@zjcc.org.cn.|Cancer Research Institute, Zhejiang Cancer Hospital, 38, Guangji Load, Hangzhou, Zhejiang, 310022, China. fengjg@zjcc.org.cn.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Feng
authors.affiliation: Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), 38, Guangji Load, Hangzhou, Zhejiang, 310022, China. seraphbaby@hotmail.com.|Cancer Research Institute, Zhejiang Cancer Hospital, 38, Guangji Load, Hangzhou, Zhejiang, 310022, China. seraphbaby@hotmail.com.
authors.forename: Shengjie
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), 38, Guangji Load, Hangzhou, Zhejiang, 310022, China. gaoy98@126.com.|Cancer Research Institute, Zhejiang Cancer Hospital, 38, Guangji Load, Hangzhou, Zhejiang, 310022, China. gaoy98@126.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), 38, Guangji Load, Hangzhou, Zhejiang, 310022, China. xxl116478471@163.com.|Department of Thoracic Surgery, Zhejiang Cancer Hospital, 38, Guangji Load, Hangzhou, Zhejiang, 310022, China. xxl116478471@163.com.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Xu
authors.affiliation: Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), 38, Guangji Load, Hangzhou, Zhejiang, 310022, China. yaoyinli9998@163.com.|Department of Thoracic Surgery, Zhejiang Cancer Hospital, 38, Guangji Load, Hangzhou, Zhejiang, 310022, China. yaoyinli9998@163.com.
authors.forename: Yinli
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), 38, Guangji Load, Hangzhou, Zhejiang, 310022, China. zhuchihong111@sina.com.|Cancer Research Institute, Zhejiang Cancer Hospital, 38, Guangji Load, Hangzhou, Zhejiang, 310022, China. zhuchihong111@sina.com.
authors.forename: Chihong
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), 38, Guangji Load, Hangzhou, Zhejiang, 310022, China. maowm1218@163.com.|Cancer Research Institute, Zhejiang Cancer Hospital, 38, Guangji Load, Hangzhou, Zhejiang, 310022, China. maowm1218@163.com.|Department of Thoracic Surgery, Zhejiang Cancer Hospital, 38, Guangji Load, Hangzhou, Zhejiang, 310022, China. maowm1218@163.com.
authors.forename: Weimin
authors.initials: W
authors.lastname: Mao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000737:chemistry*; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000737:chemistry*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry*; D004260:DNA Repair; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D011506:Proteins / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D000097722:Cohesins
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D011506:Proteins; D050796:STAT3 Transcription Factor; D000097722:Cohesins; C487465:NIPBL protein, human; C494086:STAT3 protein, human