Clinical relevance of miRNA

Currently only a limited number of biological targets has been identified, but it is widely agreed that miRNA plays an important role in a variety of biological processes, including cell death, cell growth and fat storage. The individual functions of the majority of the discovered miRNAs remain unclear and substantial research efforts are required to uncover these functions. Numerous reports emphasize however that deregulation of miRNA is involved in a number of pathological conditions, such as cancer, viral infections, metabolic diseases and neurological disorders.

As research progresses, it is to be expected that the specific role on miRNA in these conditions becomes more clear and that additional functions of miRNA and its role in other pathological conditions come to light. The findings described below provide ample motivation for further research into miRNA as well as interesting leads for the development of miRNAs for diagnostic, prognostic and therapeutic applications.

A concise overview of what is known so far.

miRNA in Cancer

The initiation and progression of cancer are two processes that may involve miRNA. In several tumor types, miRNAs have been detected, including breast, lung, colon and thyroid cancer, lymphomas and leukemia. Interestingly, miRNA sequences have been identified in parts of deleted or translocated genes in leukemia and lymphoma. In those cases, miRNA may have had a tumor suppressor function. On the other hand, other studies have shown miRNA to be expressed at a higher level in certain tumor cells. These miRNA molecules may therefore function as oncogenes. Cancer specific fingerprints of miRNA have been identified in a large number of cancer types - B-cell chronic lymphoid leukemia (B-CLL), glioblastoma and breast, lung, colon, pancreatic, thyroid, hepatocellular and gastric carcinoma. Expression profiles of miRNAs have also been shown to change during cancer progression. It is therefore likely that other hallmarks of cancer are also affected by miRNA, such tumor angiogenesis and the ability to metastasize.

Current efforts concerning the use of miRNA in oncology are mostly focused on miRNA profiling for diagnostic and prognostic purposes. InteRNA Technologies believes there are vast possiblities to apply miRNA profiling for therapeutic applications and will concentrate its efforts in this direction.

Viral infections

There is evidence that miRNA is implicated in viral infections, particularly in persistent ones. Two forms of miRNA have been described in relation to viruses. First, there are miRNAs that are encoded by the virus itself. Examples of viruses that encode miRNA are several herpes viruses, SV40, cytomegalovirus (CMV), HIV and adenovirus. The function of these miRNAs is not fully clear yet, but it seems that virus miRNA promotes latency and therefore persistency. Second, there are the host miRNAs. These also seem to play a role in viral infections; one example is miRNA-122 in the liver which has been shown to prevent viral replication of the Hepatitis C virus (HCV).

Metabolic diseases

Recent reports suggest a role for miRNA in human fat metabolism and insulin secretion. It is therefore speculated that deregulation of miRNA might be involved in diabetes and obesity, but more research is needed to gain a clear picture.

Neurological disorders

Recently, miRNA has been demonstrated to play an important role in brain development. Based on the currently available data, it is anticipated that deregulation of miRNA might also be relevant to certain neurological disorders, especially those of neurodevelopmental origin, such as schizophrenia and autism.