的miR-28-5p-IL-34-巨噬细胞反馈回路调节肝癌转移

StephenW

Hepatobiliary Malignancies
miR-28-5p-IL-34-Macrophage Feedback Loop Modulates Hepatocellular Carcinoma Metastasis
Authors
Hepatobiliary Malignancies
miR-28-5p-IL-34-Macrophage Feedback Loop Modulates Hepatocellular Carcinoma Metastasis
Authors

    Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China


    Accepted manuscript online: 11 January 2016Full publication history
    DOI: 10.1002/hep.28445View/save citation
    Cited by: 0 articles Check for new citations
    Article has an altmetric score of 3

Abstract

MicroRNAs (miRNAs) play a critical role in the regulation of tumor metastasis. The role of these molecules in hepatocellular carcinoma (HCC), however, has not been fully elucidated. In this study, we employed miRNA-sequencing and identified 22 miRNAs involved in HCC metastasis. One of these, miR-28-5p, was downregulated in HCCs. This downregulation correlated with tumor metastasis, recurrence, and poor survival. Biofunctional investigations revealed that miR-28-5p deficiency promoted tumor growth and metastasis in nude mice without altering the in vitro biological characteristics of HCC cells. Through gene expression profiles and bioinformatics analysis, we identified interleukin-34 (IL-34) as a direct target of miR-28-5p, and the effects of miR-28-5p deficiency on HCC growth and metastasis was dependent on IL-34-mediated tumor-associated macrophage (TAMs) infiltration. Moreover, we found that TAMs induced by miR-28-5p-IL-34 signaling inhibit miR-28-5p expression on HCC cells via transforming growth factor-β1 (TGF-β1), resulting in an miR-28-5p-IL-34-macrophage positive feedback loop. In clinical HCC samples, miR-28-5p levels were inversely correlated with IL-34 expression and the number of TAMs. Patients with low miR-28-5p expression, high IL-34 levels, and high numbers of TAMs had a poor prognosis with shorter overall survival (OS) and time to recurrence (TTR). Conclusion: an miR-28-5p-IL-34-macrophage feedback loop modulates HCC metastasis and serves as a novel prognostic factor as well as a therapeutic target for HCC. This article is protected by copyright. All rights reserved.

  

StephenW

肝胆恶性肿瘤
的miR-28-5p-IL-34-巨噬细胞反馈回路调节肝癌转移
作者
肝胆恶性肿瘤
的miR-28-5p-IL-34-巨噬细胞反馈回路调节肝癌转移
作者肝脏外科，复旦大学肝癌研究所，中山医院; 2016年1月11日全部公开历史DOI：10.1002 / hep.28445查看/保存引文通过引：0物品检查新引用文章癌变和肿瘤侵袭（复旦大学），教育部，上海，中国接受稿件在线重点实验室有altmetric比分3
抽象
微RNA（miRNA）在肿瘤转移的调控中起关键作用。这些分子在肝细胞癌（HCC）的作用，但是，还没有得到完全阐明。在这项研究中，我们采用的miRNA测序，并确定参与肝癌转移22的miRNA。其中的一个中，miR-28-5p，是下调的肝癌。此下调​​与肿瘤转移，复发和存活差。生物功能调查显示的miR-28-5p缺乏促进肿瘤生长和转移的裸鼠而不改变肝癌细胞的体外生物学特性。通过基因表达谱和生物信息学分析，我们发现白细胞介素34（IL-34）为的miR-28-5p的直接目标，和的miR-28-5p缺乏对肝癌生长和转移的影响是依赖于IL-34介导的肿瘤相关巨噬细胞（噬细胞）浸润。此外，我们发现，噬细胞诱导的miR-28-5p IL-34信号传导经由转化生长因子β1（TGF-β1），从而产生的miR-28-5p-IL抑制对HCC细胞的miR-28-5p表达-34，巨噬细胞的正反馈循环。在临床肝癌样品中，miR-28-5p水平呈负相关与IL-34的表达和噬的数量。患者低miR-28-5p表达，高的IL-34的水平，和高数量的TAM的具有差的预后较短的总存活（OS）和复发时间（TTR）。结论：一个的miR-28-5p IL-34细胞 - 巨噬反馈环调制肝癌转移，并作为一个新的预后因子以及用于肝癌的治疗靶点。这篇文章是受版权保护的。版权所有。