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In this article we will discuss about the major types of diseases caused by miRNA.
miRNA and Inherited Diseases:
A mutation in the seed region of miR-96 causes hereditary progressive hearing loss. A mutation in the seed region of miR-184 causes hereditary keratoconus with anterior polar cataract. Simultaneously the deletion of the miR- 17-92 cluster causes skeletal and growth defects.
miRNA and Heart Disease:
The miRNA expression profiling studies demonstrate that expression levels of specific miRNAs change in diseased human hearts, pointing to their involvement in cardiomyopathies.
Further studies on specific miRNAs in animal models have identified distinct roles for miRNAs both in the development of heart and in pathological conditions, including the regulation of key factors important forcardiogenesis, the hypertrophic growth response, and cardiac conductance.
miRNA and the nervous system:
miRNAs appear to regulate the nervous system. Neural miRNAs are involved at various stages of synaptic development, including dendritogenesis (involving miR-132, miR-134 and miR-124), synapse formation and synapse maturation (where miR-134 and miR-138 are thought to be involved). Recent studies have also revealed altered miRNA expression in schizophrenia cases.
miRNA and Viruses:
The expression of transcription activators by human herpes virus-6 DNA is believed to be regulated by viral miRNA.
miRNA and Non-Coding RNAs:
When the human genome project mapped its first chromosome in 1999, it was predicted that genome would contain over 100,000 protein coding genes. However, only around 20,000 were eventually identified (International Human Genome Sequencing Consortium, 2004).
Since then, the advent of bioinformatics approaches combined with genome tiling studies examining the transcriptome, systematic sequencing of full length cDNA libraries and experimental validation (including the creation of miRNA derived antisense oligonucleotides called antagomirs) have revealed that many transcripts are non-protein-coding RNA, including several snoRNAs and miRNAs.
miRNA and Cancer:
MicroRNAs can also act as oncogenes, directly and indirectly either by down-regulating tumour suppressors or by down-regulating genes that can act to restrict the activity of known oncogenes. Overexpression of these oncogenic miRNA may reduce protein products of tumour- suppressor genes.
On the other hand, loss of such tumour-suppressor miRNA expression may cause elevated levels of oncogenic protein. Several miRNAs have been found to have links with some types of cancer and are sometimes referred to as “oncomirs.” MicroRNA-21 was one of the first microRNAs to be identified as an oncomir.
A novel miRNA-profiling based screening assay for the detection of early-stage colorectal cancer has been developed and is currently in clinical trials. miRNA signatures may enable classification of various malignancies depending on their tissue of origin.
Another role for miRNA in cancers is to use their expression level as a prognostic. The expanding knowledge of specific roles of certain microRNAs is further contributing to our understanding of the complexity, progression and behaviour at molecular scale in oral cancer cases.
It is evident that the field of miRNAs and the study of the roles of miRNAs in oral cancer and cancers in general, is at infant stage. Yet their potentiality as therapeutic tools in management of oral cancer cases has not gone unnoticed.
A promising approach is to target oncogenic miRNAs with oligonucleotides complementary for either their mature or precursor sequence, often referred to as anti- miRNA oligonucleotides (AMOs). In future, implementation of the available information can further enhance our abilities to improve the outcome of the treatment modalities in cancer.