Abstract
BackgroundNucleolar 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).MethodsmRNA 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.ResultsmRNA 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.ConclusionsNUSAP1 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.
Highlights
Oral squamous cell carcinoma (OSCC) is a frequently occurring neoplasm that is usually aggressive and has a poor prognosis, that accounts for 275,000 new cancer cases and more than 120,000 deaths annually [1]
Results mRNA and protein expression of Nucleolar and spindle-associated protein 1 (NUSAP1) were significantly up-regulated in oral squamous cell carcinoma (OSCC)-derived cells compared with human normal oral keratinocytes (P < 0.05)
To investigate mRNA expression of NUSAP1 identified as a cancer-related gene by our previous microarray data [14], we performed quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis using 9 OSCC-derived cell lines and human normal oral keratinocytes (HNOKs)
Summary
Oral squamous cell carcinoma (OSCC) is a frequently occurring neoplasm that is usually aggressive and has a poor prognosis, that accounts for 275,000 new cancer cases and more than 120,000 deaths annually [1]. Some patients develop OSCC without risk factors, suggesting that host susceptibility plays an important role. Molecular changes in a number of oncogenes and tumor suppressor genes associated with the development of OSCC could be important clues for preventing this disease [2,5]. We previously reported gene expression profiling of OSCCs using microarray analysis to identify genes associated with oral carcinogenesis [6]. Nucleolar and spindle-associated protein 1 (NUSAP1) was detected as a significantly upregulated gene. Nucleolar and spindle-associated protein 1 (NUSAP1) is an important mitotic regulator. The aim of this study was to reveal functional mechanisms of NUSAP1 in oral squamous cell carcinoma (OSCC)
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