MicroRNA control of the metabolic response to hypoxia in malignancy

MicroRNA控制恶性肿瘤缺氧代谢反应

• 批准号: 2074389
• 金额: --
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2074389
• 关键词: MicroRNA; control; metabolic; response; hypoxia

The project will develop these initial approaches further, utilising more advanced 3D culture techniques, including spheroid and rotary cell culture. This will allow more in depth assessment of the microRNA response to varying micro-environmental conditions, including hypoxia. Laser microdissection will be used to evaluate specific tumour cell niches and assess heterogeneity of the response, both in 3D cell culture and in patient tumour specimens. Imunohistochemistry will be informed to validate results at a protein level, using already constructed in house tissue microarrays. Effects can also be analysed at a metabolic level by mass spectrometry.Functional analysis of targets will be undertaken by microRNA or gene knock in/down, with proliferation, migration and invasion assays already in use in the laboratory. Orthotopic brain tumour models are also available to allow in vivo analysis of any candidates at the late stages of the project. We will seek to repurpose any known inhibitors of the metabolic pathways interrogated to test as possible candidate agents for GBM therapy.

该项目将利用更先进的 3D 培养技术（包括球体和旋转细胞培养）进一步开发这些初步方法。这将有助于更深入地评估 microRNA 对不同微环境条件（包括缺氧）的反应。激光显微切割将用于评估 3D 细胞培养物和患者肿瘤标本中的特定肿瘤细胞生态位并评估反应的异质性。将通知免疫组织化学使用已经构建的内部组织微阵列在蛋白质水平上验证结果。还可以通过质谱法在代谢水平上分析效果。靶点的功能分析将通过 microRNA 或基因敲入/下调进行，增殖、迁移和入侵测定已在实验室中使用。原位脑肿瘤模型也可用于在项目后期对任何候选者进行体内分析。我们将寻求重新利用任何已知的代谢途径抑制剂，以测试 GBM 治疗的可能候选药物。