J Cancer 2019; 10(16):3728-3734. doi:10.7150/jca.32281

Research Paper

Centromere Protein N Participates in Cellular Proliferation of Human Oral Cancer by Cell-Cycle Enhancement

Noritoshi Oka1, Atsushi Kasamatsu2✉, Yosuke Endo-Sakamoto2, Keitaro Eizuka1, Sho Wagai1, Nao Koide-Ishida2, Isao Miyamoto2, Manabu Iyoda2, Hideki Tanzawa1,2, Katsuhiro Uzawa1,2✉

1. Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan
2. Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan

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Citation:
Oka N, Kasamatsu A, Endo-Sakamoto Y, Eizuka K, Wagai S, Koide-Ishida N, Miyamoto I, Iyoda M, Tanzawa H, Uzawa K. Centromere Protein N Participates in Cellular Proliferation of Human Oral Cancer by Cell-Cycle Enhancement. J Cancer 2019; 10(16):3728-3734. doi:10.7150/jca.32281. Available from http://www.jcancer.org/v10p3728.htm

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Abstract

Centromere protein N (CENP-N), an important member of the centromere protein family, is essential for kinetochore assembly and chromosome segregation; however, the relevance of CENP-N in cancers remains unknown. The aim of this study was to investigate CENP-N expression and its functional mechanisms in oral squamous cell carcinoma (OSCC). CENP-N expression was up-regulated significantly in vitro and in vivo in OSCCs. Overexpressed CENP-N was closely (p < 0.05) correlated with tumor growth using quantitative reverse transcriptase-polymerase chain reaction, immunoblot analysis, and immunohistochemistry. CENP-N knockdown (shCENP-N) cells showed depressed cellular proliferation by cell-cycle arrest at the G1 phase with up-regulation of p21Cip1 and p27Kip1 and down-regulation of cyclin D1, CDK2, and CDK4. Interestingly, we newly discovered that calcitriol (1, 25-dihydroxyvitamin D3) controlled the CENP-N expression level, leading to inhibition of tumor growth similar to shCENP-N cells. These results suggested that CENP-N plays a critical role in determining proliferation of OSCCs and that calcitriol might be a novel therapeutic drug for OSCCs by regulating CENP-N.

Keywords: Calcitriol, Cell-cycle arrest at G1 phase, Cellular proliferation, Centromere protein N, Oral squamous cell carcinoma