Nuclear receptor binding protein 1 correlates with better prognosis and induces caspase-dependent intrinsic apoptosis through the JNK signalling pathway in colorectal cancer.

Nuclear receptor binding protein 1 correlates with better prognosis and induces caspase-dependent intrinsic apoptosis through the JNK signalling pathway in colorectal cancer.
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核受体结合蛋白 1 与结直肠癌更好的预后相关,并通过 JNK 信号通路诱导 caspase 依赖性内在细胞凋亡

DOI:
10.1038/s41419-018-0402-7
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发表时间:
2018-04-01
影响因子:
9
通讯作者:
Wang J
Wang J
中科院分区:
生物学1区
文献类型:
--
作者:
Liao Y;Yang Z;Huang J;Chen H;Xiang J;Li S;Chen C;He X;Lin F;Yang Z;Wang J

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核受体结合蛋白1(NRBP1)是一种广泛表达的高度保守的假激酶,在细胞内稳态中起重要作用。尽管最近在理解NRBP1的生物学方面取得了进展,但NRBP1的作用及其在结直肠癌(CRC)中的潜在机制尚未完全阐明。在本研究中,我们观察到,NRBP1的表达水平显着降低,在大肠癌组织与相应的邻近正常组织相比,和高NRBP1表达与更好的预后在大肠癌。NRBP1的过表达在体内外均能抑制结直肠癌细胞的增殖并促进其凋亡。相反,NRBP1表达的敲低增加了细胞增殖并降低了凋亡细胞的百分比。此外,NRBP1的过表达激活了caspase依赖的内在凋亡。此外,我们进一步发现NRBP1通过与JNK相互作用调节凋亡途径。最后,NRBP1过表达导致异种移植小鼠模型中CRC生长减弱。我们的研究阐明了NRBP1在CRC中的抑制作用,并提供了一个潜在的治疗靶点。
Nuclear receptor binding protein 1 (NRBP1) is a ubiquitously expressed and highly conserved pseudokinase that has important roles in cellular homoeostasis. Despite recent advances in understanding the biology of NRBP1, the role of NRBP1 and its underlying mechanism in colorectal cancer (CRC) have not been fully elucidated. In the present study, we observed that NRBP1 expression levels were significantly reduced in CRC tissues compared with corresponding adjacent normal tissues, and high NRBP1 expression correlated with better prognosis in CRC. Overexpression of NRBP1 inhibited CRC cell proliferation and promoted apoptosis in vitro and in vivo. In contrast, knockdown of NRBP1 expression increased cell proliferation and decreased the percentage of apoptotic cells. Moreover, overexpression of NRBP1 activated caspase-dependent intrinsic apoptosis. In addition, we further discovered that NRBP1 regulated the apoptotic pathway through interaction with JNK. Finally, NRBP1 overexpression led to attenuated CRC growth in a xenograft mouse model. Our study illustrates the suppressor role of NRBP1 in CRC and provides a potential therapeutic target.
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