RBP-J相互作用微管相关蛋白通过激活p53-Fbxw7通路诱导人肝癌细胞凋亡并阻滞细胞周期。
RBP-J-interacting and tubulin-associated protein induces apoptosis and cell cycle arrest in human hepatocellular carcinoma by activating the p53-Fbxw7 pathway.
作者信息
Wang Haihe, Yang Zhanchun, Liu Chunbo, Huang Shishun, Wang Hongzhi, Chen Yingli, Chen Guofu
机构信息
The Key Laboratory of Molecular Diagnosis in Laboratory Medicine, Department of Pathogenobiology, Daqing Branch of Harbin Medical University, Daqing 163319, China.
Department of General Surgery of Fifth Clinical Hospital of Harbin Medical University, Daqing 163319, China.
出版信息
Biochem Biophys Res Commun. 2014 Nov 7;454(1):71-7. doi: 10.1016/j.bbrc.2014.10.023. Epub 2014 Oct 14.
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-κB 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.
在人类肝细胞癌（HCC）中观察到Notch信号异常，并且其与细胞生长的调节有关。然而，Notch信号在HCC中的作用及其潜在机制仍不清楚。RBP-J相互作用和微管相关蛋白（RITA）介导RBP-J从细胞核输出至微管纤维，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，并下调了细胞周期蛋白D1、细胞周期蛋白E、细胞周期蛋白依赖性激酶2（CDK2）、Hes-1和核因子κB p65（NF-κB p65）的表达。这些变化导致SMMC7721和HepG2细胞生长抑制，并诱导G0/G1期细胞周期阻滞和凋亡。我们的研究结果表明，RITA通过诱导G0/G1期细胞周期阻滞和凋亡在肝癌发生过程中发挥肿瘤抑制作用，并提示RITA在HCC中的治疗应用。
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