miR-148b-3p inhibits gastric cancer metastasis by inhibiting the Dock6/Rac1/Cdc42 axis.
miR-148b-3p inhibits gastric cancer metastasis by inhibiting the Dock6/Rac1/Cdc42 axis.
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miR-148b-3p通过抑制Dock6/Rac1/Cdc42轴抑制胃癌转移
DOI：
10.1186/s13046-018-0729-z
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发表时间：
2018-03-27
期刊：
影响因子：
--
通讯作者：
Liang J
中科院分区：
文献类型：
--
作者：
Li X;Jiang M;Chen D;Xu B;Wang R;Chu Y;Wang W;Zhou L;Lei Z;Nie Y;Fan D;Shang Y;Wu K;Liang J
背景我们的前期工作表明，Rho、Rac 1和Cdc 42等Rho GTP酶在胃癌中发挥重要作用，但它们在胃癌中的调控机制尚不清楚。本研究旨在探讨Dock 6在胃癌转移中的作用及其分子机制。方法采用免疫组织化学（IHC）和原位杂交（ISH）方法检测Dock 6和miR-148 b-3 p在胃癌组织和癌旁组织中的表达。采用Kaplan-Meier法和log-rank检验分析Dock 6/miR-148 b-3 p表达与胃癌患者总生存期的相关性。Dock 6和miR-148 b-3 p在胃癌中的作用通过体外和体内功能研究来研究。Rac 1和Cdc 42的激活进行了研究，通过GST下拉试验。结果Dock 6在胃癌组织中的表达明显高于癌旁组织，其阳性表达与淋巴结转移和TNM分期有关。Dock 6表达阳性的患者比Dock 6表达阴性的患者表现出更短的总生存期。Dock 6通过增加Rac 1和Cdc 42的活化促进GC迁移和侵袭。结论胃癌组织中Dock 6过表达，其阳性表达与胃癌转移有关，提示胃癌患者预后不良。miR-148 b-3 p靶向Dock 6可激活Rac 1和Cdc 42，直接影响GC细胞的运动性。靶向Dock 6-Rac 1/Cdc 42轴可以作为GC治疗的新治疗策略。
BackgroundOur previous work showed that some Rho GTPases, including Rho, Rac1 and Cdc42, play critical roles in gastric cancer (GC); however, how they are regulated in GC remains largely unknown. In this study, we aimed to investigate the roles and molecular mechanisms of Dock6, an atypical Rho guanine nucleotide exchange factor (GEF), in GC metastasis.MethodsThe expression levels of Dock6 and miR-148b-3p in GC tissues and paired nontumor tissues were determined by immunohistochemistry (IHC) and in situ hybridization (ISH), respectively. The correlation between Dock6/miR-148b-3p expression and the overall survival of GC patients was calculated by the Kaplan-Meier method and log-rank test. The roles of Dock6 and miR-148b-3p in GC were investigated by in vitro and in vivo functional studies. Rac1 and Cdc42 activation was investigated by GST pull-down assays. The inhibition of Dock6 transcription by miR-148b-3p was determined by luciferase reporter assays.ResultsA significant increase in Dock6 expression was found in GC tissues compared with nontumor tissues, and its positive expression was associated with lymph node metastasis and a higher TNM stage. Patients with positive Dock6 expression exhibited shorter overall survival periods than patients with negative Dock6 expression. Dock6 promoted GC migration and invasion by increasing the activation of Rac1 and Cdc42. miR-148b-3p expression was negatively correlated with Dock6 expression in GC, and it decreased the motility of GC cells by inhibiting the Dock6/Rac1/Cdc42 axis.ConclusionsDock6 was over-expressed in GC tissues, and its positive expression was associated with GC metastasis and indicated poor prognosis of GC patients. Targeting of Dock6 by miR-148b-3p could activate Rac1 and Cdc42, directly affecting the motility of GC cells. Targeting the Dock6-Rac1/Cdc42 axis could serve as a new therapeutic strategy for GC treatment.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
3.7
作者：
Miyamoto, Yuki;Yamauchi, Junji;Tanoue, Akito
通讯作者：
Tanoue, Akito
影响因子：
10.5
作者：
Laurin M;Côté JF
通讯作者：
Côté JF
影响因子：
4
作者：
Ding X;Liu J;Liu T;Ma Z;Wen D;Zhu J
通讯作者：
Zhu J
RhoE 通过抑制 Bax 增强胃癌细胞的多药耐药性。
DOI：
10.1016/j.bbrc.2008.12.044
发表时间：
2009-02-06
影响因子：
3.1
作者：
Li, Kai;Lu, Yuanyuan;Fan, Daiming
通讯作者：
Fan, Daiming