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核受体结合蛋白 1 与结直肠癌的较好预后相关,并通过 JNK 信号通路诱导 caspase 依赖的内在细胞凋亡。

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

机构信息

Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 510655, Guangzhou, People's Republic of China.

Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, 510655, Guangzhou, People's Republic of China.

出版信息

Cell Death Dis. 2018 Apr 1;9(4):436. doi: 10.1038/s41419-018-0402-7.

Abstract

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.

摘要

核受体结合蛋白 1(NRBP1)是一种广泛表达且高度保守的假激酶,在细胞内稳态中具有重要作用。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 在 CRC 组织中的表达水平明显低于相应的相邻正常组织,并且 NRBP1 的高表达与 CRC 的更好预后相关。NRBP1 的过表达在体外和体内均抑制 CRC 细胞增殖并促进细胞凋亡。相反,NRBP1 表达的下调增加了细胞增殖并降低了凋亡细胞的百分比。此外,过表达 NRBP1 激活了依赖半胱天冬酶的内在凋亡途径。此外,我们还发现 NRBP1 通过与 JNK 相互作用调节凋亡途径。最后,NRBP1 的过表达导致异种移植小鼠模型中 CRC 生长减弱。我们的研究说明了 NRBP1 在 CRC 中的抑制作用,并提供了一个潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4103/5864759/6cd2964dc766/41419_2018_402_Fig3_HTML.jpg

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