Mir-92 Micro RNA Precursor Family - Clinical Implications

Clinical Implications

From the investigations that have been reviewed in this article we can draw some direction as to how miR-92 could have important clinical implications. Thanks to the level of diversity in miRNA expression across cancers, using them as a diagnosis and classification tool has serious potential. The modest number of miRNAs present in the genome and in specific profiling experiments allow for highly resolved patterns without overly complex data sets. As an example, a set of miRNA profiles of well differentiated cancers was used to train a decision algorithm for application on another set of poorly differentiated tumours (for which clinical diagnosis is normally established by anatomical means). Successful diagnosis of the test set was significantly increased.

Apart from diagnosis and characterisation of cancers, there is also therapeutic value to the discovery of miR-92s involvement in essential cell physiology and in promoting cancer. Returning to our review of breast cancer, the isoform ERβ1 is well studied as having anti-proliferative effects and pro-apoptotic effects. We discussed that miR-92 targets and down regulates ERβ1, and evidence suggests that miR-92 is regulated by oestrogen which is upstream of the ERβ1. Evidence for this was demonstrated by growing MCF-7 cells in oestrogen depleted conditions and adding antagonists to the oestrogen receptors: Tamoxifen and E2. miR-92 was upregulated in response, suggesting that the likely oncogenic role for miR-92 in this context is inhibition of ERβ1 expression in the presence of oestrogen. Thus, a therapeutic strategy against breast cancer could be aimed at re-activating expression of ERβ1 through manipulation of miR-92 expression.

For HCC patients (discussed in the previous section), quantitative real time PCR (qRT-PCR) demonstrated a reduction of miR-92a in the plasma against healthy blood samples. This bares similarities to the discoveries made by profiling leukaemia patients (also discussed in the previous section). The expression differences in both cases was relative to miR-638 levels. miR-638 is an miRNA that seems to have a consistent presence in human blood plasma and may be physiologically necessary. This demonstrates that a decrease in the miR-92a:miR-638 ratio in human plasma may serve as a valuable diagnostic marker not only for leukaemia but also for solid tumours such as HCC.

In respect to the Medullablastoma studies, therapeutic strategy could include using antigomirs against the oncomir-1 cluster in patients harbouring an aberrant SHH/PATCHED pathway.