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

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.