Investigating the Role of Antisense RNA in the CCL3/CCR5/RALY Pathway

研究反义 RNA 在 CCL3/CCR5/RALY 通路中的作用

• 批准号: 2611968
• 金额: --
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2611968
• 关键词: Investigating; Role; Antisense; RNA; CCL3

The CCL3/CCR5/RALY pathway is a pathway involved in numerous cell functions with dysregulation seen in various diseases such as cancer. One study showed that tumour-associated macrophages in lung cancer had increased expression of CCR5 and of targets downstream of this receptor. Another study showed how increased expression of CCR5 and other proteins in this pathway is linked to a better prognosis in lung adenocarcinoma patients. The precise mechanism of this signalling pathway and its involvement in disease is still not characterised, but antisense RNA may play a role. CCL3, CCR5 and RALY have antisense transcripts termed CCL3-AS1, CCR5AS and RALY-AS1 respectively. Dysregulation of antisense RNAs has been observed in almost every type of cancer, with both pro- and anti-tumour effects being seen, so understanding the mechanism by which these antisenses are interacting is important. It has been demonstrated that CCR5AS was able to bind and inhibit RALY which is an RNA binding protein responsible for the degradation of CCR5 mRNA, but the other two antisenses have a currently unknown function. Designing a system which can allow for the knockdown or enhancement of these antisense transcripts would allow for the corresponding changes to be reported and further investigated. The data generated suggests that such a system may have been found for RALY-AS1, allowing for an investigation into the mechanism to take place.

CCL3/CCR5/RALY通路参与多种细胞功能失调，在多种疾病（如癌症）中可见。一项研究表明，肺癌肿瘤相关巨噬细胞CCR5及其受体下游靶点的表达增加。另一项研究表明，CCR5和该途径中其他蛋白的表达增加与肺腺癌患者更好的预后有关。这种信号通路的确切机制及其在疾病中的作用尚不清楚，但反义RNA可能起作用。CCL3、CCR5和RALY有反义转录本，分别称为CCL3- as1、CCR5AS和RALY- as1。在几乎所有类型的癌症中都观察到反义rna的失调，具有促肿瘤和抗肿瘤的作用，因此了解这些反义rna相互作用的机制非常重要。已经证明CCR5AS能够结合并抑制RALY， RALY是一种负责CCR5 mRNA降解的RNA结合蛋白，但其他两种反义蛋白的功能目前尚不清楚。设计一个能够抑制或增强这些反义转录本的系统，将允许报告和进一步研究相应的变化。所产生的数据表明，可能已经为rally - as1找到了这样一个系统，从而可以对其机制进行调查。