CCDC34 is up-regulated in bladder cancer and regulates bladder cancer cell proliferation, apoptosis and migration.
CCDC34 is up-regulated in bladder cancer and regulates bladder cancer cell proliferation, apoptosis and migration.
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CCDC34 在膀胱癌中上调并调节膀胱癌细胞增殖、凋亡和迁移
DOI：
10.18632/oncotarget.4624
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发表时间：
2015-09-22
期刊：
影响因子：
--
通讯作者：
Guo Y
中科院分区：
文献类型：
--
作者：
Gong Y;Qiu W;Ning X;Yang X;Liu L;Wang Z;Lin J;Li X;Guo Y
卷曲螺旋是一种超螺旋结构蛋白，具有多种生物学功能，其异常表达与肿瘤细胞的迁移、侵袭和转移表型有直接关系。本研究的目的是探讨含有卷曲螺旋结构域的蛋白34（CCDC 34）在膀胱癌发生中的关键作用，迄今为止尚未有报道。在此，我们发现CCDC 34在膀胱癌组织和细胞系中表达升高。慢病毒介导的siRNA干扰CCDC 34基因可显著抑制膀胱癌细胞的增殖和迁移，诱导细胞周期阻滞于G2/M期，并增加细胞凋亡。此外，CCDC 34敲低抑制裸鼠膀胱肿瘤生长。此外，CCDC 34沉默还降低了MEK、ERK 1/2、JNK、p38和Akt的磷酸化以及c-Raf和c-Jun的表达，表明MAPK和AKT途径（ERK/MAPK、p38/MAPK、JNK/MAPK和PI 3 K/Akt）可能参与了CCDC 34对膀胱癌细胞增殖和迁移的调节。我们的研究结果首次揭示了CCDC 34在膀胱癌发病机制中的潜在致癌作用，它可能作为膀胱癌的生物标志物甚至治疗靶点。
The coiled coil is a superhelical structural protein motif involved in a diverse array of biological functions, and the abnormal expression of the coiled-coil domain containing proteins has a direct link with the phenotype of tumor cell migration, invasion and metastasis. The aim of this study was to investigate the critical role of Coiled-coil domain-containing protein 34 (CCDC34) in bladder carcinogenesis, which has never been reported to date. Here, we found CCDC34 expression was elevated in bladder cancer tissues and cell lines. The knockdown of CCDC34 via lentivirus-mediated siRNA significantly suppressed bladder cancer cells proliferation and migration, and induced cell cycle arrest at G2/M phase and increased apoptosis in vitro. In addition, CCDC34 knockdown suppressed bladder tumor growth in nude mice. Moreover, CCDC34 silencing decreased the phosphorylation of MEK, ERK1/2, JNK, p38 and Akt, and the expressions of c-Raf and c-Jun, indicating MAPK and AKT pathways (ERK/MAPK, p38/MAPK, JNK/MAPK and PI3K/Akt) might be involved in CCDC34 regulation of bladder cancer cell proliferation and migration. Our findings revealed for the first time a potential oncogenic role for CCDC34 in bladder carcinoma pathogenesis and it may serve as a biomarker or even a therapeutic target for bladder cancer.