Disruption of the CCDC43-FHL1 interaction triggers apoptosis in gastric cancer cells
Disruption of the CCDC43-FHL1 interaction triggers apoptosis in gastric cancer cells
复制标题
CCDC43-FHL1 相互作用的破坏引发胃癌细胞凋亡
DOI：
10.1016/j.yexcr.2022.113107
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发表时间：
2022-03-22
影响因子：
3.7
通讯作者：
Wang，Jide
中科院分区：
文献类型：
--
作者：
Chen，Yaying;Pei，Miaomiao;Wang，Jide
螺旋卷曲结构域蛋白43(CCDC43)在促进胃癌细胞增殖和侵袭中起重要作用，而四个半LIM结构域1(FHL1)参与了胃癌细胞的凋亡。我们试图解决CCDC43和FHL1在调控GC细胞生长和凋亡中的相互关系。免疫印迹、免疫荧光检测蛋白表达水平。采用EDU法、平板集落形成法、Matrigel侵袭法和动物模型对其体外和体内功能进行了评价。流式细胞仪和Hoechst 33258染色检测细胞凋亡率。互易免疫共沉淀(co-IP)分析表明CCDC43与FHL1在物理上相互作用。CCDC43的表达与FHL1呈负相关。此外，CCDC43的上调导致FHL1水平下降，反之亦然。与CCDC43组相比，CCDC43联合FHL1组可显著降低GC细胞的生长、转移和侵袭能力。此外，siRNA介导的CCDC43抑制导致FHL1解离，从而抑制GC细胞的增殖和转移。CCDC43抑制介导了FHL1蛋白的稳定性。此外，CCDC43还与FHL1相互作用。CCDC43+FHL1过表达抑制胃癌细胞的增殖和迁移，并诱导其在体内外的凋亡。
The coiled-coil domain-containing protein 43 (CCDC43) is essential to promote gastric cancer (GC) proliferation and invasion, while four and a half LIM domains 1 (FHL1) involves GC cells apoptosis. We attempted to address inter-relationship between CCDC43 and FHL1 in modulating GC cells growth and apoptosis. Levels of protein expression were assessed by western blot, immunofluorescence. Using EdU, plate colony formation, Matrigel invasion and animal models, we evaluated the function in vitro and in vivo. Apoptosis was evaluated by flow cytometry and Hoechst 33258 staining. Reciprocal co-immunoprecipitation (co-IP) analyses indicated that CCDC43 physically interacted with FHL1. The expression of CCDC43 was negatively correlated with FHL1. Moreover, up-regulation of CCDC43 resulted in FHL1 level decline, and the reverse is also true. CCDC43 expressed jointly with FHL1 group significantly decreases the ability of the growth, metastasis and invasion of GC cells compared with that of the CCDC43 group. Furthermore, siRNA-mediated repression of CCDC43 results in dissociation from FHL1 and causes suppression of GC cell proliferation and metastasis. CCDC43 repression mediates the stability of FHL1 protein. In addition, CCDC43 interacts with FHL1. Knockdown of CCDC43 plus FHL1 overexpression inhibits proliferation and migration and induces apoptosis of GC cells in vitro andvivo.