RBP-J-interacting and tubulin-associated protein induces apoptosis and cell cycle arrest in human hepatocellular carcinoma by activating the p53-Fbxw7 pathway
RBP-J-interacting and tubulin-associated protein induces apoptosis and cell cycle arrest in human hepatocellular carcinoma by activating the p53-Fbxw7 pathway
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DOI：
10.1016/j.bbrc.2014.10.023
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发表时间：
2014-11-07
影响因子：
3.1
通讯作者：
Chen, Guofu
中科院分区：
文献类型：
--
作者：
Wang, Haihe;Yang, Zhanchun;Chen, Guofu
Notch信号异常在人肝细胞癌中被观察到，并与细胞生长调控有关。然而，Notch信号在肝细胞癌中的作用及其潜在机制仍不清楚。RBP-J相互作用和微管蛋白相关(RITA)介导RBP-J向微管蛋白纤维的核输出，并下调Notch介导的转录。在本研究中，我们发现RITA过表达增加了P53和Fbxw7的蛋白表达，下调了Cyclin D1、Cyclin E、CDK2、Hes-1和NF-kappa B p65的表达。这些变化导致SMMC7721和HepG2细胞的生长抑制，并诱导G0/G1期细胞周期停滞和凋亡。我们的研究结果表明，RITA通过诱导G0/G1期细胞周期停滞和细胞凋亡而在肝癌发生中发挥抑瘤作用，并提示RITA在肝癌治疗中的应用。(C)2014 Elsevier Inc.保留所有权利。
Aberrant Notch signaling is observed in human hepatocellular carcinoma (HCC) and has been associated with the modulation of cell growth. However, the role of Notch signaling in HCC and its underlying mechanism remain elusive. RBP-J-interacting and tubulin-associated (RITA) mediates the nuclear export of RBP-J to tubulin fibers and downregulates Notch-mediated transcription. In this study, we found that RITA overexpression increased protein expression of p53 and Fbxw7 and downregulated the expression of cyclin D1, cyclin E, CDK2, Hes-1 and NF-kappa B p65. These changes led to growth inhibition and induced G0/G1 cell cycle arrest and apoptosis in SMMC7721 and HepG2 cells. Our findings indicate that RITA exerts tumor-suppressive effects in hepatocarcinogenesis through induction of G0/G1 cell cycle arrest and apoptosis and suggest a therapeutic application of RITA in HCC. (C) 2014 Elsevier Inc. All rights reserved.