Dr Laura Denby: Long Noncoding RNA Is a Good Biomarker for Acute Kidney Injury

The role of long noncoding RNA in the pathophysiology of kidney disease is better understood now and they seem to be a good biomarker for distinguishing people with more severe acute kidney injury, said Laura Denby, PhD, Kidney Research UK Senior Fellow, senior lecturer and principal investigator in the Centre for Cardiovascular Science at the University of Edinburgh.

Transcript

Long noncoding RNA are showing promise as biomarkers for a variety of diseases. How are they used as diagnostic biomarkers and where are we with current use of noncoding RNA in clinical practice?

Long noncoding RNA are really interesting, because we've been able to detect them know where we didn't, obviously, appreciate their role in the pathophysiology of diseases, and we're able to detect them. Therefore, they seem to be quite specific to diseases. So, therefore, that suggests they might make a good biomarker and you might be able to use them to distinguish between people that maybe have a more severe injury than another.

In terms of the current use of noncoding RNA in clinical practice, I think the use of the smaller noncoding RNAs, which are very stable, has moved forward, has been quite good biomarkers; for example, miR [microRNA]-122 in paracetamol overdose have been quite rapidly considered useful in that concept. So, I think the smaller have moved forward quicker, and the long noncoding I'm sure will follow.

How does the research and use of long noncoding RNA in kidney disease compare with other diseases?

With the advent of all this sort of single-cell transcriptomic sequencing and our ability to do precision medicine, where we can look at like individual patients and consider what therapy they might need, noncoding RNA has been really interesting, because what they do is they regulate the expression of genes and they regulate pathways. So, therefore, they can almost be thought of as polypharmacy, if you will, because you could target just one microRNA, you target many pathways, where previously you might have had to give a drug for each of those pathways. So, in that respect, they're quite exciting.

The key, in terms of making sure that it's precise and good, is making sure we've got the best microRNA and the best context, and also when we want to manipulate it, making sure we're getting it to the correct cell and it's having its effect localized to the cell type.

What new technologies are making it possible to take the knowledge of noncoding RNA's role in the pathophysiology of kidney disease and turn it into actual therapeutic approaches?

In terms of the noncoding RNA, we've obviously moved forward. We’re able to do sequencing for them in terms of the long RNA species. We're able to use some of the new long-range sequencing technologies, which allows us to understand far better their presence if there's different isoforms of them, for example. So, therefore, the sequencing modalities have really made a difference to our understanding of what they're doing.

In terms of our ability to knock them up and down, there are quite good pharmacological agents for doing this. So, we can very selectively do that now in cells and begin to do it in tissue. So, this makes it easier to understand what their biology is and therefore design the appropriate type of therapeutic that you might want to move toward clinical use.