NCYM在人MYCN扩增的神经母细胞瘤细胞中促进钙蛋白酶介导的Myc切口产生。
NCYM promotes calpain-mediated Myc-nick production in human MYCN-amplified neuroblastoma cells.
作者信息
Shoji Wataru, Suenaga Yusuke, Kaneko Yoshiki, Islam S M Rafiqul, Alagu Jennifer, Yokoi Sana, Nio Masaki, Nakagawara Akira
机构信息
Division of Biochemistry and Innovative Cancer Therapeutics and Children's Cancer Research Center, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba 260-8717, Japan; Department of Pediatric Surgery, Graduate School of Medicine, Tohoku University, Sendai 980-8574, Japan.
Division of Biochemistry and Innovative Cancer Therapeutics and Children's Cancer Research Center, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba 260-8717, Japan; Cancer Genome Center, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba 260-8717, Japan.
出版信息
Biochem Biophys Res Commun. 2015 Jun 5;461(3):501-6. doi: 10.1016/j.bbrc.2015.04.050. Epub 2015 Apr 17.
NCYM is a cis-antisense gene of MYCN and is amplified in human neuroblastomas. High NCYM expression is associated with poor prognoses, and the NCYM protein stabilizes MYCN to promote proliferation of neuroblastoma cells. However, the molecular mechanisms of NCYM in the regulation of cell survival have remained poorly characterized. Here we show that NCYM promotes cleavage of MYCN to produce the anti-apoptotic protein, Myc-nick, both in vitro and in vivo. NCYM and Myc-nick were induced at G2/M phase, and NCYM knockdown induced apoptotic cell death accompanied by Myc-nick downregulation. These results reveal a novel function of NCYM as a regulator of Myc-nick production in human neuroblastomas.
NCYM是MYCN的一个顺式反义基因，在人类神经母细胞瘤中发生扩增。NCYM高表达与预后不良相关，且NCYM蛋白可稳定MYCN以促进神经母细胞瘤细胞增殖。然而，NCYM在细胞存活调控中的分子机制仍不清楚。在此我们表明，NCYM在体外和体内均促进MYCN的裂解以产生抗凋亡蛋白Myc-nick。NCYM和Myc-nick在G2/M期被诱导，且敲低NCYM会诱导凋亡性细胞死亡并伴有Myc-nick下调。这些结果揭示了NCYM在人类神经母细胞瘤中作为Myc-nick产生调节因子的新功能。
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