Inflammatory microRNAs in liver cancer

肝癌中的炎症性 microRNA

• 批准号: 230854839
• 负责人: Professor Dr. Frank Lammert
• 金额: --
• 依托单位: Signal Transduction Laboratory
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/230854839?language=en
• 关键词: Inflammatory; microRNAs; liver; cancer

Chronic inflammation is one of the hallmarks of cancer. Hepatocellular carcinoma (HCC), responsible for > 0.5 million deaths worldwide per annum, is closely related to chronic inflammation, commonly caused by hepatitis B or C virus infections or steatohepatitis. Interleukin-6, an inflammatory cytokine, which signals via Jak/STAT3, often shows increased activity in HCC. In addition, expression levels of certain miRNAs (small non-coding RNAs, which negatively regulate gene expression) are also altered in HCC and other cancers. Here, we aim to investigate the role of miRNAs in the regulation of IL-6/Jak/STAT3 signalling in hepatoma cells and non-transformed hepatocytes. We will not only study intracellular miRNAs, but will pay special attention to secreted miRNAs, isolated from blood samples. Potential targets of selected miRNAs shall be identified by detailed analysis and validation of corresponding mRNA expression data. In an independent approach, we will study miRNAs targeting key players of the IL-6 signal transduction cascade (e.g. STAT3, SOCS3). Results obtained with cell lines will be translated to samples from HCC patients (blood, tumour tissue, surrounding liver tissue) and to primary hepatocytes isolated from these patients. The project will increase our knowledge on the relevance of intracellular and secreted miRNAs in inflammatory signal transduction. We expect moreover that our approach will lead to the identification of (a) miRNAs, which could be targeted therapeutically to modulate IL-6/STAT3 signal transduction and (b) miRNAs, which may be eventually used as biomarkers in the diagnosis and prognosis of HCC. This would be most useful in the surveillance of risk patients with chronic hepatitis or liver cirrhosis to better predict potential progression into HCC at an early stage when treatment success rates are still favourable.

慢性炎症是癌症的标志之一。肝细胞癌 (HCC) 每年导致全球超过 50 万人死亡，它与慢性炎症密切相关，通常由乙型或丙型肝炎病毒感染或脂肪性肝炎引起。 Interleukin-6 是一种炎症细胞因子，通过 Jak/STAT3 发出信号，在 HCC 中通常表现出活性增强。此外，某些 miRNA（负向调节基因表达的小非编码 RNA）的表达水平在 HCC 和其他癌症中也会发生改变。在这里，我们的目的是研究 miRNA 在肝癌细胞和非转化肝细胞中 IL-6/Jak/STAT3 信号传导调节中的作用。我们不仅会研究细胞内 miRNA，还会特别关注从血液样本中分离出来的分泌型 miRNA。应通过详细分析和验证相应 mRNA 表达数据来确定所选 miRNA 的潜在靶标。我们将采用独立的方法研究针对 IL-6 信号转导级联关键参与者（例如 STAT3、SOCS3）的 miRNA。细胞系获得的结果将转化为 HCC 患者的样本（血液、肿瘤组织、周围肝组织）以及从这些患者分离的原代肝细胞。该项目将增加我们对细胞内和分泌的 miRNA 在炎症信号转导中的相关性的了解。此外，我们预计我们的方法将导致鉴定（a）miRNA，其可在治疗上靶向调节IL-6/STAT3信号转导和（b）miRNA，其最终可用作诊断和预后中的生物标志物肝癌。这对于监测患有慢性肝炎或肝硬化的高危患者非常有用，以便在治疗成功率仍然较高的早期阶段更好地预测潜在的 HCC 进展。

项目成果

ID: 194: Role of microRNAs in signal transduction pathways of the inflammatory cytokine Interleukin-6: Relevance for liver diseases

ID：194：microRNA 在炎症细胞因子 Interleukin-6 信号转导途径中的作用：与肝脏疾病的相关性

• DOI: 10.1016/j.cyto.2015.08.198
• 期刊: Cytokine
• 影响因子: 3.8
• 作者: Servais; F.A.; M. Kirchmeyer; M. Hamsdorf; C. Haan; M. Casper; F. Lammert; P. Nazarov; L. Vallar; S. Kreis;I. Behrmann
• 通讯作者: I. Behrmann

Role of microRNAs in signal transduction pathways of the inflammatory cytokine interleukin-6 in hepatocellular carcinoma cell lines and primary hepatocytes

microRNA在肝细胞癌细胞系和原代肝细胞炎症细胞因子白细胞介素6信号转导通路中的作用

• DOI: 10.1016/s0959-8049(16)61630-1
• 发表时间: 2016
• 期刊: European Journal of Cancer
• 影响因子: 8.4
• 作者: Servais; F.; M. Kirchmeyer; M. Casper; M. Hamdorf; C. Haan; P. Nazarov; L. Vallar; C. Rubie; M. Glanemann; F. Lammert; S. Kreis; I. Behrmann
• 通讯作者: I. Behrmann

ID: 202: IL-27 elicits responses similar to Interferon-gamma in non-hematopoietic cells

ID：202：IL-27 在非造血细胞中引发类似于干扰素-γ 的反应

• DOI: 10.1016/j.cyto.2015.08.206
• 期刊: Cytokine
• 影响因子: 3.8
• 作者: Rolvering; C.; A. Zimmer; I. Behrmann; C. Haan
• 通讯作者: C. Haan

Cytokines and hepatocellular carcinoma: Potential progression markers and cell typespecific modulators of the mirnome (Interleukin-6 and JAK/STAT activating cytokines)

细胞因子和肝细胞癌：微小组的潜在进展标记物和细胞类型特异性调节剂（Interleukin-6 和 JAK/STAT 激活细胞因子）

• DOI: 10.1055/s-0036-1597466
• 发表时间: 2016
• 期刊: Zeitschrift für Gastroenterologie
• 作者: Kirchmeyer; M.; F. A. Servais; M. Hamdorf; C. Haan; P. Nazarov; L. Vallar; M. Casper; M. Glanemann; A. Arslanow; C. Rubie; F. Lammert; S. Kreis; I. Behrmann
• 通讯作者: I. Behrmann

Evaluation der pro-steatotischen Genvariante rs641738 im MBOAT7-Gen bei Patienten mit hepatozellulärem Karzinom (HCC)

肝细胞癌 (HCC) 患者 MBOAT7 基因中促脂肪变性基因变异 rs641738 的评估

• DOI: 10.1055/s-0036-1597467
• 发表时间: 2016
• 期刊: Zeitschrift für Gastroenterologie
• 作者: Casper; M.; M. Krawczyk; I. Behrmann; M. Glanemann;F. Lammert
• 通讯作者: F. Lammert