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

CCL 3/CCR 5/RALY通路是参与许多细胞功能的通路，在各种疾病如癌症中观察到失调。一项研究表明，肺癌中的肿瘤相关巨噬细胞增加了CCR 5和该受体下游靶点的表达。另一项研究表明，CCR 5和该途径中其他蛋白质的表达增加与肺腺癌患者的预后更好有关。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可能发挥作用。CCL 3、CCR 5和RALY具有反义转录物，分别称为CCL 3-AS 1、CCR 5AS和RALY-AS 1。几乎在每种类型的癌症中都观察到反义RNA的失调，可以看到促肿瘤和抗肿瘤作用，因此了解这些反义RNA相互作用的机制很重要。研究表明，CCR 5AS能够结合并抑制RALY，RALY是一种负责CCR 5 mRNA降解的RNA结合蛋白，但其他两种反义物的功能目前尚不清楚。设计一个系统，可以允许敲低或增强这些反义转录本将允许相应的变化被报告和进一步研究。生成的数据表明，RALY-AS 1可能已经发现了这样的系统，从而可以对该机制进行调查。

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.