Overexpression of a novel osteopetrosis-related gene CCDC154 suppresses cell proliferation by inducing G2/M arrest
Overexpression of a novel osteopetrosis-related gene CCDC154 suppresses cell proliferation by inducing G2/M arrest
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DOI：
10.4161/cc.21642
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发表时间：
2012-09-01
期刊：
影响因子：
4.3
通讯作者：
Lu, Xincheng
中科院分区：
文献类型：
--
作者：
Liao, Wanqin;Zhao, Rongsen;Lu, Xincheng
骨质疏松症是一种骨骼疾病，可导致儿童死亡。我们之前描述了一种新的自发常染色体隐性骨质疏松小鼠突变体，“新无牙”（ntl）。在这项研究中，我们首次报道了含有CCDC154 （coil -coil domain containing 154）的新基因的鉴定、克隆和鉴定，CCDC154基因的缺失与ntl突变体完全相关，该基因缺失的5kb序列包括外显子1-6。CCDC154基因在小鼠和人之间具有保守性，在小鼠组织中广泛表达。CCDC154的细胞定位在早期核内体。过表达CCDC154通过诱导G(2)/M阻滞抑制HEK293细胞的增殖。CCDC154还能抑制肿瘤细胞的生长，软琼脂实验显示，转染CCDC154后，Hela细胞的集落大小明显减少。我们的研究结果表明，CCDC154是一种新的与骨硬化相关的基因，参与细胞周期调控和肿瘤抑制生长。
Osteopetrosis, a disorder of skeletal bone, can cause death during childhood. We previously described a new spontaneous autosomal recessive osteopetrosis mouse mutant, "new toothless" (ntl). In this study, we reported for the first time the identification, cloning and characterization of the coiled-coil domain-containing 154 (CCDC154), a novel gene whose deletion of similar to 5 kb sequence including exons 1-6 was completely linked to the ntl mutant. The CCDC154 was conserved between mouse and human and is wildly expressed in mouse tissues. The cellular localization of CCDC154 was in the early endosomes. Overexpression of CCDC154 inhibited cell proliferation of HEK293 cells by inducing G(2)/M arrest. CCDC154 also inhibited tumor cell growth, and the soft agar assay revealed a significant decrease of the colony size of Hela cells upon transfection of CCDC154. Our results indicate that CCDC154 is a novel osteopetrosis-related gene involved in cell cycle regulation and tumor suppression growth.