RRC ID 45494
Author Okamoto A, Higo M, Shiiba M, Nakashima D, Koyama T, Miyamoto I, Kasama H, Kasamatsu A, Ogawara K, Yokoe H, Tanzawa H, Uzawa K.
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.
Journal PLoS One
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.
Volume 10(11)
Pages e0142252
Published 2015-1-1
DOI 10.1371/journal.pone.0142252
PII PONE-D-15-29330
PMID 26554377
PMC PMC4640814
MeSH Antineoplastic Agents, Phytogenic / pharmacology* Antineoplastic Agents, Phytogenic / therapeutic use Apoptosis / drug effects Apoptosis / genetics Biomarkers, Tumor / genetics Carcinoma, Squamous Cell / drug therapy Carcinoma, Squamous Cell / genetics* Carcinoma, Squamous Cell / pathology Cell Cycle / drug effects Cell Cycle / genetics Cell Line, Tumor Cell Proliferation / drug effects Cell Proliferation / genetics* Down-Regulation Gene Expression Regulation, Neoplastic* Humans Microtubule-Associated Proteins / genetics* Microtubule-Associated Proteins / metabolism Mouth Neoplasms / drug therapy Mouth Neoplasms / genetics* Mouth Neoplasms / pathology Paclitaxel / pharmacology* Paclitaxel / therapeutic use
IF 2.74
Times Cited 22
Human and Animal Cells HSC-2(RCB1945) HSC-3(RCB1975) HSC-4(RCB1902) Ca9-22(RCB1976) Sa3(RCB0980) HO-1-u-1(RCB2102)