title: Increased SHP-1 expression results in radioresistance, inhibition of cellular senescence, and cell cycle redistribution in nasopharyngeal carcinoma cells.
abstract: BACKGROUND
  Radioresistance is the main limit to the efficacy of radiotherapy in nasopharyngeal carcinoma (NPC). SHP-1 is involved in cancer progression, but its role in radioresistance and senescence of NPC is not well understood. This study aimed to assess the role of SHP-1 in the radioresistance and senescence of NPC cells.
  
  
  METHODS
  SHP-1 was knocked-down and overexpressed in CNE-1 and CNE-2 cells using lentiviruses. Cells were irradiated to observe their radiosensitivity by colony forming assay. BrdU incorporation assay and flow cytometry were used to monitor cell cycle. A β-galactosidase assay was used to assess senescence. Western blot was used to assess SHP-1, p21, p53, pRb, Rb, H3K9Me3, HP1γ, CDK4, cyclin D1, cyclin E, and p16 protein expressions.
  
  
  RESULTS
  Compared with CNE-1-scramble shRNA cells, SHP-1 downregulation resulted in increased senescence (+107%, P < 0.001), increased radiosensitivity, higher proportion of cells in G0/G1 (+33%, P < 0.001), decreased expressions of CDK4 (-44%, P < 0.001), cyclin D1 (-41%, P = 0.001), cyclin E (-97%, P < 0.001), Rb (-79%, P < 0.001), and pRb (-76%, P = 0.001), and increased expression of p16 (+120%, P = 0.02). Furthermore, SHP-1 overexpression resulted in radioresistance, inhibition of cellular senescence, and cell cycle arrest in the S phase. Levels of p53 and p21 were unchanged in both cell lines (all P > 0.05).
  
  
  CONCLUSIONS
  SHP-1 has a critical role in radioresistance, cell cycle progression, and senescence of NPC cells. Down-regulating SHP-1 may be a promising therapeutic approach for treating patients with NPC.
authors.affiliation: Cancer Center, Union hosipital, Wuhan, 430022, Hubei Province, China. 26877345@qq.com.
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Cancer Center, Union hosipital, Wuhan, 430022, Hubei Province, China. 798342014@qq.com.|Cancer center, Affliated Hospital of Guangdong Medical College, Zhanjiang, 524001, Guangdong Province, China. 798342014@qq.com.
authors.forename: Xiaofen
authors.initials: X
authors.lastname: Pan
authors.affiliation: Cancer Center, Union hosipital, Wuhan, 430022, Hubei Province, China. zouzhenwei1983@126.com.
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Zou
authors.affiliation: Cancer Center, Union hosipital, Wuhan, 430022, Hubei Province, China. dingqiansci@126.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Cancer Center, Union hosipital, Wuhan, 430022, Hubei Province, China. xhzlwg@163.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
authors.affiliation: Cancer Center, Union hosipital, Wuhan, 430022, Hubei Province, China. penggangsci@sina.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Peng
mesh_terms: D015153:Blotting, Western; D002277:Carcinoma; D002453:Cell Cycle; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000235:genetics*; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D006801:Humans; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000473:pathology*; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000096:biosynthesis*; D011836:Radiation Tolerance / Q000235:genetics*
chemical_list: C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6