September 2019

Defining the Role of the MicroRNA-184: Argonaute 2 axis in Psoriasis

Dr Kehinde Ross is a Senior Lecturer in Biochemistry and Cell Biology at Liverpool John Moores University. His work focusses on the roles of microRNA in psoriasis and other skin diseases and the development of RNA-directed therapies.

Here Kehinde summarises the research findings from his British Skin Foundation funded research.

Summary

Complex diseases like psoriasis are underpinned by defective control of genes and cell behaviour. These genes include microRNAs, which fine-tune the biomolecular trajectories of cells. We previously found that microRNA-184 (miR-184) levels were relatively high in psoriatic skin and that miR-184 reduced the amount of an important biomolecule, argonaute 2 (AGO2).

Some research suggests the AGO2 molecules act as a brake on cell growth by moving into cell nuclei and blocking growth genes. If miR-184 depletes AGO2, skin cells could end up growing faster than normal. Such enhanced growth of skin cells is a feature of psoriatic skin. Hence, in this project, we examined miR-184 and AGO2 in skin cells to better understand their relationships cellular processes important in skin health.

What did we find?

• the levels of miR-184 were indeed raised in psoriatic lesions compared to non-lesional skin
• levels of AGO2 were not convincingly reduced in psoriatic lesions
• miR-184 slowed down rather than accelerated the growth of skin cells
• miR-184 also supported specialised processes (of differentiation) that enable skin function
• AGO2 migrated into cell nuclei under certain conditions
• Nuclear AGO2 does not seem to block growth genes in keratinocytes

Altogether, our findings indicate that miR-184 is important player in maintaining normal skin processes. However, elevated levels of miR-184 in psoriatic skin may be a compensatory mechanism that does not impinge effectively on AGO2 or AGO2-related deceleration of cell growth.

How does this help people with psoriasis in the long term?

More studies are needed but our findings may underpin the development or validation of future psoriasis therapies in the emerging RNA-based medicines framework. In addition, the nuclear localisation of AGO2 can potentially be exploited for the enhancement of RNA-based therapies that may work in cell nuclei to counteract skin inflammation. 

We would like to thank the British Skin Foundation for supporting this study.

Dr Kehinde Ross

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Image credit: Jari Louhelainen