KIF11 promotes cell proliferation via ERBB2/PI3K/AKT signaling pathway in gallbladder cancer.
KIF11 promotes cell proliferation via ERBB2/PI3K/AKT signaling pathway in gallbladder cancer.
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KIF 11通过ERBB 2/PI 3 K/AKT信号通路促进胆囊癌细胞增殖
DOI：
10.7150/ijbs.54074
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发表时间：
2021
影响因子：
9.2
通讯作者：
Jun G
中科院分区：
文献类型：
--
作者：
Wei D;Rui B;Qingquan F;Chen C;Ping HY;Xiaoling S;Hao W;Jun G
胆囊癌是一种相对罕见但致命的恶性肿瘤，其显著特征之一是细胞增殖。本研究的目的是探讨候选hub基因对胆囊癌增殖和肿瘤发生的生物学影响及其分子机制。我们分析了差异表达的基因以及这些基因与MKI 67之间的相关性，并表明KIF 11是胆囊癌（GBC）增殖的主要上调调节因子之一。Gene Ontology、Gene Sets Enrichment Analysis和KEGG Pathway分析表明KIF 11可能通过ERBB 2/PI 3 K/AKT信号通路促进GBC细胞增殖。功能获得和功能丧失实验表明，KIF 11在体外可调节GBC细胞周期和癌细胞增殖。KIF 11的特异性抑制剂Monastrol处理后，GBC细胞出现G2 M期细胞周期阻滞，细胞增殖和克隆形成能力降低。异种移植模型显示KIF 11促进GBC体内生长。拯救实验表明KIF 11诱导GBC细胞增殖依赖于ERBB 2/PI 3 K/AKT通路。此外，我们发现H3 K27 ac信号在UCSC基因组浏览器数据库中的KIF 11启动子区域中富集。差异表达分析显示，EP 300，一个主要的组蛋白乙酰转移酶修饰H3 K27 ac信号，在胆囊癌中高表达，相关性分析表明，EP 300与KIF 11在几乎所有的癌症类型呈正相关。我们进一步发现，组蛋白乙酰化抑制剂处理后，KIF 11以剂量依赖性和时间依赖性的方式显著下调。目前的结果强调了KIF 11高表达通过ERBB 2/PI 3 K/AKT信号通路促进GBC细胞增殖。这些发现有助于加深我们对GBC癌症发生机制的理解，并有助于开发新的诊断和治疗靶点。
Proliferation is one of the significant hallmarks of gallbladder cancer, which is a relatively rare but fatal malignance. Aim of this study was to examine the biological impact and molecular mechanism of the candidate hub-gene on the proliferation and tumorigenesis of gallbladder cancer. We analyzed the differentially expressed genes and the correlation between these genes with MKI67, and showed that KIF11 is one of the major upregulated regulators of proliferation in gallbladder cancer (GBC). The Gene Ontology, Gene Sets Enrichment Analysis and KEGG Pathway analysis indicated that KIF11 may promote GBC cell proliferation through the ERBB2/PI3K/AKT signaling pathway. Gain-of-function and loss-of-function assay demonstrated that KIF11 regulated GBC cell cycle and cancer cell proliferation in vitro. GBC cells exhibited G2M phase cell cycle arrest, cell proliferation and clone formation ability reduction after treatment with Monastrol, a specific inhibitor of KIF11. Xenograft model showed that KIF11 promotes GBC growth in vivo. Rescue experiments showed that KIF11-induced GBC cell proliferation dependented on ERBB2/PI3K/AKT pathway. Moreover, we found that H3K27ac signals are enriched among the promoter region of KIF11 in the UCSC Genome Browser Database. Differentially expressed analysis showed that EP300, a major histone acetyltransferase modifying H3K27ac signal, is highly expressed in gallbladder cancer and correlation analysis illustrated that EP300 is positively related with KIF11 in almost all the cancer types. We further found that KIF11 was significantly downregulated in a dose-dependent and time-dependent manner after histone acetylation inhibitor treatment. The present results highlight that high KIF11 expression promotes GBC cell proliferation through the ERBB2/PI3K/AKT signaling pathway. The findings may help deepen our understanding of mechanism underlying GBC cancer development and development of novel diagnostic and therapeutic target.
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影响因子：
3.5
作者：
Albrecht, Thomas;Rausch, Melina;Goeppert, Benjamin
通讯作者：
Goeppert, Benjamin
DOI：
10.1083/jcb.201303163
发表时间：
2013-07-22
期刊：
The Journal of cell biology
影响因子：
--
作者：
Wakana Y;Villeneuve J;van Galen J;Cruz-Garcia D;Tagaya M;Malhotra V
通讯作者：
Malhotra V
影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
影响因子：
17.1
作者：
Venere M;Horbinski C;Crish JF;Jin X;Vasanji A;Major J;Burrows AC;Chang C;Prokop J;Wu Q;Sims PA;Canoll P;Summers MK;Rosenfeld SS;Rich JN
通讯作者：
Rich JN
影响因子：
4
作者：
Song T;Zheng Y;Wang Y;Katz Z;Liu X;Chen S;Singer RH;Gu W
通讯作者：
Gu W