Oka Noritoshi, Kasamatsu Atsushi, Endo-Sakamoto Yosuke, Eizuka Keitaro, Wagai Sho, Koide-Ishida Nao, Miyamoto Isao, Iyoda Manabu, Tanzawa Hideki, Uzawa Katsuhiro
Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan.
Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
J Cancer. 2019 Jun 9;10(16):3728-3734. doi: 10.7150/jca.32281. eCollection 2019.
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 and 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 p21 and p27 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.
着丝粒蛋白N(CENP-N)是着丝粒蛋白家族的重要成员,对动粒组装和染色体分离至关重要;然而,CENP-N在癌症中的相关性仍不清楚。本研究的目的是探讨CENP-N在口腔鳞状细胞癌(OSCC)中的表达及其功能机制。在OSCC中,CENP-N表达显著上调。使用定量逆转录聚合酶链反应、免疫印迹分析和免疫组织化学方法,过表达的CENP-N与肿瘤生长密切相关(p<0.05)。CENP-N敲低(shCENP-N)细胞通过细胞周期阻滞在G1期,导致细胞增殖受抑,同时p21和p27上调,细胞周期蛋白D1、细胞周期蛋白依赖性激酶2(CDK2)和细胞周期蛋白依赖性激酶4(CDK4)下调。有趣的是,我们新发现骨化三醇(1,25-二羟基维生素D3)可控制CENP-N表达水平,从而导致肿瘤生长受到抑制,类似于shCENP-N细胞。这些结果表明,CENP-N在决定OSCC细胞增殖中起关键作用,并且骨化三醇可能通过调节CENP-N成为OSCC的一种新型治疗药物。