title: Down-Regulation of Nucleolar and Spindle-Associated Protein 1 (NUSAP1) Expression Suppresses Tumor and Cell Proliferation and Enhances Anti-Tumor Effect of Paclitaxel in Oral Squamous Cell Carcinoma.
abstract: BACKGROUND
  Nucleolar and spindle-associated protein 1 (NUSAP1) is an important mitotic regulator. In addition to its crucial function in mitosis, NUSAP1 has recently received attention due to the interesting roles in carcinogenesis. The aim of this study was to reveal functional mechanisms of NUSAP1 in oral squamous cell carcinoma (OSCC).
  
  
  METHODS
  mRNA and protein expression levels of NUSAP1 in 9 OSCC-derived cells were analyzed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and immunoblotting analyses. The correlation between the NUSAP1 expression profile and the clinicopathological factors was evaluated by immunohistochemistry (IHC) in clinical OSCC samples (n = 70). The NUSAP1 knockdown cells were established with short hairpin RNA (shRNA) in OSCC cells, and functional assays were performed using these cells. In addition to the evaluation of cellular proliferation and cell cycle, we also investigated the potential role of NUSAP1 in paclitaxel (PTX)-induced cellular responses.
  
  
  RESULTS
  mRNA and protein expression of NUSAP1 were significantly up-regulated in OSCC-derived cells compared with human normal oral keratinocytes (P < 0.05). IHC revealed that NUSAP-1 expression is closely associated with primary advanced T stage (P<0.05). Suppression of NUSAP1 expression levels led to significant (P < 0.05) inhibition of cellular proliferation. Furthermore, apoptosis induced by PTX was enhanced in NUSAP1 knockdown OSCC cells.
  
  
  CONCLUSIONS
  NUSAP1 may be a crucial biomarker for OSCC. Moreover, down-regulated NUSAP1 expression suppresses tumor proliferation and also enhances anti-tumor effect of PTX by activating apoptotic pathways. Thus, the present study strongly suggests that regulating NUSAP1 expression should contribute to the therapy for OSCC.
authors.affiliation: Department of Oral Science, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okamoto
authors.affiliation: Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chuo-ku, Chiba, Japan.
authors.forename: Morihiro
authors.initials: M
authors.lastname: Higo
authors.affiliation: Department of Oral Science, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan.|Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Shiiba
authors.affiliation: Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chuo-ku, Chiba, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Nakashima
authors.affiliation: Department of Oral Science, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan.
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Koyama
authors.affiliation: Department of Oral Science, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Miyamoto
authors.affiliation: Department of Oral Science, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kasama
authors.affiliation: Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chuo-ku, Chiba, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kasamatsu
authors.affiliation: Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chuo-ku, Chiba, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Ogawara
authors.affiliation: Department of Oral and Maxillofacial Surgery Research Institute, National Defense Medical College Hospital, Tokorozawa-shi, Saitama, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Yokoe
authors.affiliation: Department of Oral Science, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan.|Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chuo-ku, Chiba, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Tanzawa
authors.affiliation: Department of Oral Science, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan.|Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chuo-ku, Chiba, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Uzawa
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D008869:Microtubule-Associated Proteins; C000709213:NUSAP1 protein, human; D017239:Paclitaxel