miR-146b-5p inhibits tumorigenesis and metastasis of gallbladder cancer by targeting Toll-like receptor 4 via the nuclear factor-κB pathway
miR-146b-5p inhibits tumorigenesis and metastasis of gallbladder cancer by targeting Toll-like receptor 4 via the nuclear factor-κB pathway
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DOI：
10.3892/or.2021.7966
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发表时间：
2021-04-01
期刊：
影响因子：
4.2
通讯作者：
Ji, Wu
中科院分区：
文献类型：
--
作者：
Ouyang, Bin;Pan, Ningfeng;Ji, Wu
胆囊癌（GBC）是一种胆道癌，在发展中国家很常见，死亡率很高。本研究的目的是探讨GBC发生和发展的机制。首先在 GBC 组织中观察到 miR-146b-5p 表达减少，其靶基因 Toll 样受体 4 (TLR4) 表达增加。进一步研究表明，miR-146b-5p 表达减少导致 TLR4 表达增加，导致核因子 (NF)-kappa B 信号传导激活。体外培养GBC细胞，观察到miR-146b-5p的过表达有效抑制其活力、增殖、迁移和侵袭，并增加其凋亡。使用 BALB/c 裸鼠异种移植模型，证明 miR-146b-5p 的过表达足以减小肿瘤体积并减轻病理特征。总体而言，本研究结果表明，miR-146b-5p表达的减少增加了TLR4的表达，并间接激活了NF-κB信号通路，从而调节GBC的发生。
Gallbladder cancer (GBC) is a carcinoma of the biliary tract, which is common in developing countries and is associated with a high fatality rate. The aim of the present study was to investigate the mechanisms underlying the occurrence and development of GBC. A decrease in the expression of miR-146b-5p and an increase in the expression of its target gene Toll-like receptor 4 (TLR4) were first observed in GBC tissues. Further study demonstrated that an increase in TLR4 expression caused by a decrease in miR-146b-5p expression led to activation of nuclear factor (NF)-kappa B signaling. GBC cells were cultured in vitro, and it was observed that overexpression of miR-146b-5p effectively inhibited their viability, proliferation, migration and invasion, and increased their apoptosis. Using a BALB/c nude mouse xenograft model, it was demonstrated that overexpression of miR-146b-5p was sufficient to reduce tumor volume and alleviate pathological characteristics. Overall, the results of the present study indicated that the decrease in the expression of miR-146b-5p increased TLR4 expression and indirectly activated the NF-kappa B signaling pathway, thereby regulating the development of GBC.