Inhibition of KLHL21 prevents cholangiocarcinoma progression through regulating cell proliferation and motility, arresting cell cycle and reducing Erk activation
Inhibition of KLHL21 prevents cholangiocarcinoma progression through regulating cell proliferation and motility, arresting cell cycle and reducing Erk activation
复制标题
抑制 KLHL21 可通过调节细胞增殖和运动、阻止细胞周期和减少 Erk 激活来防止胆管癌进展。
DOI：
10.1016/j.bbrc.2018.03.152
复制
发表时间：
2018-05-15
影响因子：
3.1
通讯作者：
Song, Penghong
中科院分区：
文献类型：
--
作者：
Chen, Jian;Song, Wenfeng;Song, Penghong
kelch样家族成员21（KLHL21）参与细胞有丝分裂和运动。然而，KLHL21在胆管癌（CCA）中的临床意义和生物学功能尚不清楚。这是第一项描述KLHL21在CCA进展中关键作用的研究。与配对的正常胆管组织相比，KLHL21在CCA组织中的表达升高。此外，免疫组化和统计分析表明，KLHL21的表达与肿瘤组织学分级呈负相关（p < 0.05），与患者的总生存期呈负相关（p < 0.01）。在CCA细胞中，我们发现抑制KLHL21可显著降低增殖、迁移和侵袭。进一步的结果表明，抑制KLHL21引发G0/G1细胞周期阻滞，导致P21和P27表达增加以及细胞周期蛋白E1表达降低，最终导致CCA细胞增殖受抑制。此外，KLHL21敲低通过降低磷酸化 - Erk1/2的表达减轻了Erk信号通路的激活。我们的数据表明，KLHL21在CCA的肿瘤发生和进展中起重要作用，这意味着它可能作为CCA治疗的潜在治疗靶点。（C）2018爱思唯尔公司。保留所有权利。
Kelch-like family member 21 (KLHL21) is involved in cell mitosis and motility. Nevertheless, the clinical significance and biological function of KLHL21 in cholangiocarcinoma (CCA) are elusive. This is the first study to describe a pivotal role for KLHL21 in the progression of CCA. The expression of KLHL21 was elevated in CCA tissues compared with paired normal bile duct tissues. In addition, immunohistochemical and statistical analyses demonstrated that the expression of KLHL21 correlated inversely with tumor histological grade (p < 0.05) and the overall survival of patients (p < 0.01). In CCA cells, we found that the inhibition of KLHL21 significantly reduced proliferation, migration and invasion. Further results indicated that inhibition of KLHL21 triggered G0/G1 cell cycle arrest, leading to the increased expression of P21 and P27 and decreased expression of Cyclin El, which eventually resulted in proliferation suppression in CCA cells. Furthermore, KLHL21 knockdown alleviated the activation of the Erk signaling pathway via decreasing the expression of phospho-Erk1/2. Our data demonstrated that KLHL21 plays an essential role in the tumorigenesis and progression of CCA, implying that it might serve as a potential therapeutic target for CCA treatment. (C) 2018 Elsevier Inc. All rights reserved.