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

被引:24
作者
Oka, Noritoshi [1 ]
Kasamatsu, Atsushi [2 ]
Endo-Sakamoto, Yosuke [2 ]
Eizuka, Keitaro [1 ]
Wagai, Sho [1 ]
Koide-Ishida, Nao [2 ]
Miyamoto, Isao [2 ]
Iyoda, Manabu [2 ]
Tanzawa, Hideki [1 ,2 ]
Uzawa, Katsuhiro [1 ,2 ]
机构
[1] Chiba Univ, Grad Sch Med, Dept Oral Sci, Chiba, Japan
[2] Chiba Univ Hosp, Dept Dent & Oral Maxillofacial Surg, Chiba, Japan
来源
JOURNAL OF CANCER | 2019年 / 10卷 / 16期
关键词
Calcitriol; Cell-cycle arrest at G1 phase; Cellular proliferation; Centromere protein N; Oral squamous cell carcinoma; CENP-A NUCLEOSOMES; EXPRESSION; CARCINOMA; RECOGNITION; PHENOTYPE; TARGET;
D O I
10.7150/jca.32281
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 p21(Cip1) and p27(Kip1) 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.
引用
收藏
页码:3728 / 3734
页数:7
相关论文
共 35 条
[1]   CENP-A nucleosomes localize to transcription factor hotspots and subtelomeric sites in human cancer cells [J].
Athwal, Rajbir K. ;
Walkiewicz, Marcin P. ;
Baek, Songjoon ;
Fu, Song ;
Bui, Minh ;
Camps, Jordi ;
Ried, Thomas ;
Sung, Myong-Hee ;
Dalal, Yamini .
EPIGENETICS & CHROMATIN, 2015, 8
[2]   Centromere assembly requires the direct recognition of CENP-A nucleosomes by CENP-N [J].
Carroll, Christopher W. ;
Silva, Mariana C. C. ;
Godek, Kristina M. ;
Jansen, Lars E. T. ;
Straight, Aaron F. .
NATURE CELL BIOLOGY, 2009, 11 (07) :896-U297
[3]   Molecular architecture of the kinetochore-microtubule interface [J].
Cheeseman, Iain M. ;
Desai, Arshad .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2008, 9 (01) :33-46
[4]   KIF14 is a candidate oncogene in the 1q minimal region of genomic gain in multiple cancers [J].
Corson, TW ;
Huang, A ;
Tsao, MS ;
Gallie, BL .
ONCOGENE, 2005, 24 (30) :4741-4753
[5]   Deficient Spindle Assembly Checkpoint in Multiple Myeloma [J].
Diaz-Rodriguez, Elena ;
Alvarez-Fernandez, Stela ;
Chen, Xi ;
Paiva, Bruno ;
Lopez-Perez, Ricardo ;
Luis Garcia-Hernandez, Juan ;
San Miguel, Jesus F. ;
Pandiella, Atanasio .
PLOS ONE, 2011, 6 (11)
[6]   Sarcoendoplasmic reticulum Ca2+ ATPase type 2 downregulated in human oral squamous cell carcinoma [J].
Endo, Y ;
Uzawa, K ;
Mochida, Y ;
Shiiba, M ;
Bukawa, H ;
Yokoe, H ;
Tanzawa, H .
INTERNATIONAL JOURNAL OF CANCER, 2004, 110 (02) :225-231
[7]   Structural transitions of centromeric chromatin regulate the cell cycle-dependent recruitment of CENP-N [J].
Fang, Junnan ;
Liu, Yuting ;
Wei, Yun ;
Deng, Wenqiang ;
Yu, Zhouliang ;
Huang, Li ;
Teng, Yan ;
Yao, Ting ;
You, Qinglong ;
Ruan, Haihe ;
Chen, Ping ;
Xu, Rui-Ming ;
Li, Guohong .
GENES & DEVELOPMENT, 2015, 29 (10) :1058-1073
[8]   Phosphorylation of AIB1 at Mitosis Is Regulated by CDK1/CYCLIN B [J].
Ferrero, Macarena ;
Ferragud, Juan ;
Orlando, Leonardo ;
Valero, Luz ;
Sanchez del Pino, Manuel ;
Farras, Rosa ;
Font de Mora, Jaime .
PLOS ONE, 2011, 6 (12)
[9]   The nuclear vitamin D receptor: Biological and molecular regulatory properties revealed [J].
Haussler, MR ;
Whitfield, GK ;
Haussler, CA ;
Hsieh, JC ;
Thompson, PD ;
Selznick, SH ;
Dominguez, CE ;
Jurutka, PW .
JOURNAL OF BONE AND MINERAL RESEARCH, 1998, 13 (03) :325-349
[10]   CENP-C/H/I/K/M/T/W/N/L and hMis12 but not CENP-S/X participate in complex formation in the nucleoplasm of living human interphase cells outside centromeres [J].
Hoischen, Christian ;
Yavas, Sibel ;
Wohland, Thorsten ;
Diekmann, Stephan .
PLOS ONE, 2018, 13 (03)