BRD7 Promotes Cell Proliferation and Tumor Growth Through Stabilization of c-Myc in Colorectal Cancer.
BRD7 Promotes Cell Proliferation and Tumor Growth Through Stabilization of c-Myc in Colorectal Cancer.
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BRD7 通过稳定结直肠癌中的 c-Myc 促进细胞增殖和肿瘤生长
DOI：
10.3389/fcell.2021.659392
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发表时间：
2021
影响因子：
5.5
通讯作者：
Zhou M
中科院分区：
文献类型：
--
作者：
Zhao R;Liu Y;Wu C;Li M;Wei Y;Niu W;Yang J;Fan S;Xie Y;Li H;Wang W;Zeng Z;Xiong W;Li X;Li G;Zhou M
BRD 7在许多恶性肿瘤中作为重要的肿瘤抑制因子发挥作用。然而，BRD 7对结直肠癌（CRC）进展的影响仍然未知。在此，基于我们先前工作中构建的BRD 7敲除（BRD 7-/-）和BRD 7 flox/flox（BRD 7 +/+）小鼠模型，我们建立了氧化偶氮甲烷/葡聚糖硫酸钠（AOM/DSS）诱导的小鼠模型。BRD 7 +/+小鼠对AOM/DSS诱导的结肠炎相关CRC高度易感，BRD 7显著促进细胞增殖和细胞周期G1/S转换，但对细胞凋亡无显著影响。此外，BRD 7与c-Myc相互作用并通过抑制其泛素-蛋白酶体依赖性降解来稳定c-Myc。此外，在BRD 7沉默的CRC细胞中恢复c-Myc的表达在体外和体内恢复了细胞增殖、细胞周期进展和肿瘤生长。此外，BRD 7和c-Myc在CRC患者中均显著上调，并且这些蛋白的高表达与CRC患者的临床分期和不良预后相关。总的来说，BRD 7作为癌基因发挥作用，并通过调节c-Myc蛋白的泛素-蛋白酶体依赖性稳定来促进CRC进展。靶向BRD 7/c-Myc轴可能是CRC的潜在治疗策略。
BRD7 functions as a crucial tumor suppressor in numerous malignancies. However, the effects of BRD7 on colorectal cancer (CRC) progression are still unknown. Here, based on the BRD7 knockout (BRD7–/–) and BRD7flox/flox (BRD7+/+) mouse models constructed in our previous work, we established an azoxymethane/dextran sodium sulfate (AOM/DSS)-induced mouse model. BRD7+/+ mice were found to be highly susceptible to AOM/DSS-induced colitis-associated CRC, and BRD7 significantly promoted cell proliferation and cell cycle G1/S transition but showed no significant effect on cell apoptosis. Furthermore, BRD7 interacted with c-Myc and stabilized c-Myc by inhibiting its ubiquitin–proteasome-dependent degradation. Moreover, restoring the expression of c-Myc in BRD7-silenced CRC cells restored cell proliferation, cell cycle progression, and tumor growth in vitro and in vivo. In addition, BRD7 and c-Myc were both significantly upregulated in CRC patients, and high expression of these proteins was associated with clinical stage and poor prognosis in CRC patients. Collectively, BRD7 functions as an oncogene and promotes CRC progression by regulating the ubiquitin–proteasome-dependent stabilization of c-Myc protein. Targeting the BRD7/c-Myc axis could be a potential therapeutic strategy for CRC.
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影响因子：
8
作者：
Jung, Ji Hoon;Jung, Deok-Beom;Kim, Sung-Hoon
通讯作者：
Kim, Sung-Hoon
影响因子：
11.5
作者：
Park, Young-Ae;Lee, Jeong-Won;Bae, Duk-Soo
通讯作者：
Bae, Duk-Soo
影响因子：
8
作者：
Liu T;Zhao M;Liu J;He Z;Zhang Y;You H;Huang J;Lin X;Feng XH
通讯作者：
Feng XH
BRD7表达和c-Myc激活形成双负反馈环，通过靶向致癌miR-141控制鼻咽癌的细胞增殖和肿瘤生长
DOI：
10.1186/s13046-018-0734-2
发表时间：
2018-03-20
影响因子：
11.3
作者：
Liu, Yukun;Zhao, Ran;Zhou, Ming
通讯作者：
Zhou, Ming
影响因子：
16.6
作者：
Clark, Peter G. K.;Vieira, Lucas C. C.;Dixon, Darren J.
通讯作者：
Dixon, Darren J.