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

CCL3/CCR5/RALY通路是一条参与多种细胞功能的通路，在癌症等多种疾病中可见调节失调。一项研究表明，肺癌中的肿瘤相关巨噬细胞增加了CCR5和该受体下游靶点的表达。另一项研究表明，CCR5和其他蛋白在这一途径中的高表达与肺腺癌患者更好的预后有关。这一信号通路的确切机制及其与疾病的关系尚不清楚，但反义RNA可能起到一定作用。CCL3、CCR5和RALY分别具有反义转录本CCL3-AS1、CCR5AS和RALY-AS1。几乎在每种类型的癌症中都观察到了反义RNA的调节失调，既有促肿瘤作用，也有抗肿瘤作用，因此了解这些反义RNA相互作用的机制是很重要的。已经证明CCR5AS能够结合并抑制RALY，RALY是一种RNA结合蛋白，负责CCR5mRNA的降解，但另外两种反义蛋白的功能目前尚不清楚。设计一种能够敲除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。产生的数据表明，可能已经为RALY-AS1发现了这样一个系统，从而允许对其机制进行调查。

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.