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miR-146b-5p 通过核因子-κB 通路靶向 Toll 样受体 4 抑制胆囊癌的发生和转移。

miR‑146b‑5p inhibits tumorigenesis and metastasis of gallbladder cancer by targeting Toll‑like receptor 4 via the nuclear factor‑κB pathway.

机构信息

Research Institute of General Surgery, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, Jiangsu 210002, P.R. China.

Department of Neurology, Nanjing Central Hospital, Nanjing, Jiangsu 210018, P.R. China.

出版信息

Oncol Rep. 2021 Apr;45(4). doi: 10.3892/or.2021.7966. Epub 2021 Mar 2.

DOI:10.3892/or.2021.7966
PMID:33649824
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7877004/
Abstract

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)‑κB signaling. GBC cells were cultured , 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‑κB signaling pathway, thereby regulating the development of GBC.

摘要

胆囊癌(GBC)是一种胆道癌,在发展中国家较为常见,且死亡率较高。本研究旨在探讨 GBC 发生和发展的机制。首先在 GBC 组织中观察到 miR-146b-5p 表达降低和其靶基因 Toll 样受体 4(TLR4)表达增加。进一步的研究表明,miR-146b-5p 表达降低导致 TLR4 表达增加,从而激活核因子(NF)-κB 信号通路。培养 GBC 细胞后,观察到 miR-146b-5p 的过表达可有效抑制其活力、增殖、迁移和侵袭,并促进其凋亡。使用 BALB/c 裸鼠异种移植模型,证明 miR-146b-5p 的过表达足以降低肿瘤体积并减轻病理特征。综上所述,本研究结果表明,miR-146b-5p 的表达降低增加了 TLR4 的表达,并间接激活了 NF-κB 信号通路,从而调节 GBC 的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f2/7877004/650977d7bf09/or-45-04-7966-g08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f2/7877004/847b2da2073f/or-45-04-7966-g00.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f2/7877004/f1a9ccf0d137/or-45-04-7966-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f2/7877004/2373efb569df/or-45-04-7966-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f2/7877004/26570965662f/or-45-04-7966-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f2/7877004/85a975aa2488/or-45-04-7966-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f2/7877004/4c01b941d936/or-45-04-7966-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f2/7877004/1a2ad6c69918/or-45-04-7966-g07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f2/7877004/650977d7bf09/or-45-04-7966-g08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f2/7877004/847b2da2073f/or-45-04-7966-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f2/7877004/a29693293d25/or-45-04-7966-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f2/7877004/f1a9ccf0d137/or-45-04-7966-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f2/7877004/2373efb569df/or-45-04-7966-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f2/7877004/26570965662f/or-45-04-7966-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f2/7877004/85a975aa2488/or-45-04-7966-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f2/7877004/4c01b941d936/or-45-04-7966-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f2/7877004/1a2ad6c69918/or-45-04-7966-g07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9f2/7877004/650977d7bf09/or-45-04-7966-g08.jpg

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