Blood Serum From Head and Neck Squamous Cell Carcinoma Patients Induces Altered MicroRNA and Target Gene Expression Profile in Treated Cells.

Blood Serum From Head and Neck Squamous Cell Carcinoma Patients Induces Altered MicroRNA and Target Gene Expression Profile in Treated Cells.
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头部和颈部鳞状细胞癌患者的血清诱导了治疗细胞中的microRNA和靶基因表达谱。

DOI:
10.3389/fonc.2018.00217
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发表时间:
2018
影响因子:
4.7
通讯作者:
Masternak MM
Masternak MM
中科院分区:
医学3区
文献类型:
--
作者:
Allen B;Schneider A;Victoria B;Nunez Lopez YO;Muller M;Szewczyk M;Pazdrowski J;Majchrzak E;Barczak W;Golusinski W;Golusinski P;Masternak MM

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头颈部鳞状细胞癌(HNSCC)是人类最常见的癌症之一。全世界每年有近60万例新诊断,超过一半的确诊患者将无法生存。鉴于这种低存活率,开发用于HNSCC的新型基于细胞的测定将允许用于每个个体患者的特异性诊断的更多机械方法。基于细胞的测定将提供更多的信息数据,预测治疗患者的细胞过程,这实际上将改善患者随访。更重要的是,它将提高治疗方法的特异性和有效性。在这项研究中,我们研究了HNSCC患者血清对体外暴露细胞中microRNA(miRNA)表达的调节作用。下一代miRNA测序显示,HNSCC患者血清诱导的miRNA表达谱与健康个体血清不同。在检测到的377个miRNA中,我们发现当比较暴露于来自HNSCC或健康个体的血清的细胞时,16个miRNA差异表达。基因本体分析和通路分析显示这些miRNA靶基因参与了肿瘤相关的生物学过程,包括细胞周期和细胞凋亡。实时荧光定量PCR分析显示,HNSCC患者血清下调了5个与肿瘤发生有关的基因的表达水平,其中P53和SLC2A1是检测到的miRNAs的直接靶基因。这些新的发现为循环中的癌症相关因子如何调节远端细胞中有利于肿瘤发生的基因和调控元件的表达提供了新的见解。这有可能用于新的治疗方法和更特异性的诊断,其中肿瘤特异性细胞系或单细胞体外测定用于个性化治疗和早期检测原发性肿瘤或转移。
The head and neck squamous cell carcinoma (HNSCC) represents one of the most common cancers in humans. Close to 600,000 new diagnoses are made every year worldwide and over half of diagnosed patients will not survive. In view of this low survival rate, the development of novel cell-based assays for HNSCC will allow more mechanistic approaches for specific diagnostics for each individual patient. The cell-based assays will provide more informative data predicting cellular processes in treated patient, which in effect would improve patient follow up. More importantly, it will increase the specificity and effectiveness of therapeutic approaches. In this study, we investigated the role of serum from HNSCC patients on the regulation of microRNA (miRNA) expression in exposed cells in vitro. Next-generation sequencing of miRNA revealed that serum from HNSCC patients induced a different miRNA expression profile than the serum from healthy individuals. Out of 377 miRNA detected, we found that 16 miRNAs were differentially expressed when comparing cells exposed to serum from HNSCC or healthy individuals. The analysis of gene ontologies and pathway analysis revealed that these miRNA target genes were involved in biological cancer-related processes, including cell cycle and apoptosis. The real-time PCR analysis revealed that serum from HNSCC patients downregulate the expression level of five genes involved in carcinogenesis and two of these genes—P53 and SLC2A1—are direct targets of detected miRNAs. These novel findings provide new insight into how cancer-associated factors in circulation regulate the expression of genes and regulatory elements in distal cells in favor of tumorigenesis. This has the potential for new therapeutic approaches and more specific diagnostics with tumor-specific cell lines or single-cell in vitro assays for personalized treatment and early detection of primary tumors or metastasis.
DOI: 10.1093/nar/gkq1027
发表时间: 2011-01
影响因子: 14.9
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DOI: 10.1002/stem.1619
发表时间: 2014-04
期刊: STEM CELLS
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期刊: Journal of experimental & clinical cancer research : CR
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DOI: 10.1158/0008-5472.can-11-0241
发表时间: 2011-08-01
期刊: CANCER RESEARCH
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发表时间: 2010-04-01
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