title: Overexpression of CIP2A is an independent prognostic indicator in nasopharyngeal carcinoma and its depletion suppresses cell proliferation and tumor growth.
abstract: BACKGROUND
  Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that acts as a prognostic marker for several human malignancies. In this study, we investigated the clinical significance of CIP2A and its function in nasopharyngeal carcinoma (NPC).
  
  
  METHODS
  Quantitative RT-PCR, western blot, and immunohistochemistry analyses were used to quantify CIP2A expression in NPC cell lines and clinical samples. Kaplan-Meier curves were used to estimate the association between CIP2A expression and patient survival. The functional role of CIP2A in NPC cell lines was evaluated by small interfering RNA-mediated depletion of the protein followed by analyses of cell proliferation and xenograft growth.
  
  
  RESULTS
  CIP2A levels were upregulated in NPC cell lines and clinical samples at both the mRNA and protein levels (P < 0.01). Patients with high CIP2A expression had poorer overall survival (HR, 1.98; 95% CI, 1.16-3.34; P = 0.01) and poorer disease-free survival (HR, 1.68; 95% CI, 1.07-2.62; P = 0.02) rates than patients with low CIP2A expression. In addition, CIP2A expression status was an independent prognostic indicator for NPC patients. The depletion of CIP2A expression inhibited c-Myc protein expression in NPC cell lines, suppressed cell viability, colony formation, and anchorage-independent growth in vitro, and inhibited xenograft tumor growth in vivo.
  
  
  CONCLUSIONS
  Our data demonstrate that high CIP2A expression in patients was associated with poor survival in NPC, and depletion of CIP2A expression inhibited NPC cell proliferation and tumor growth. Thus, these results warrant further investigation of CIP2A as a novel therapeutic target for the treatment of NPC.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.forename: Qing-Mei
authors.initials: QM
authors.lastname: He
authors.forename: Jie-Wei
authors.initials: JW
authors.lastname: Chen
authors.forename: Ying-Qin
authors.initials: YQ
authors.lastname: Li
authors.forename: Ya-Fei
authors.initials: YF
authors.lastname: Xu
authors.forename: Xian-Yue
authors.initials: XY
authors.lastname: Ren
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Hai-Qiang
authors.initials: HQ
authors.lastname: Mai
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Shao
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Jia
authors.forename: Tie-Bang
authors.initials: TB
authors.lastname: Kang
authors.forename: Mu-Sheng
authors.initials: MS
authors.lastname: Zeng
authors.affiliation: Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng Road East, Guangzhou, People's Republic of China. majun2@mail.sysu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001324:Autoantigens / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009368:Neoplasm Transplantation; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016019:Survival Analysis; D047368:Tumor Burden; D059016:Tumor Microenvironment
chemical_list: D001324:Autoantigens; D014408:Biomarkers, Tumor; C500266:CIP2A protein, human; D047908:Intracellular Signaling Peptides and Proteins; C489427:MYC protein, human; D008565:Membrane Proteins; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering