[3] Most miRNAs are grouped into clusters in the human genome or within families that share functions, expression profiles, promoters, or are incorporated into the same ribonucleic protein.
[3][6] miRNAs can be oncogenes or tumor suppressor genes depending on their targets while mir-92 has been implicated as the former in leukaemia forms AML and ALL, Hepatocellular carcinoma (HCC) and several other cancers.
Some circulating miRNAs are specific to tumour patients, while miR-92 on the other-hand is present in healthy individuals in the serum, but levels are variable and appear to change in response to the onset of some cancers.
[3] The miRNAs of oncomir-1 and its paralogs are likely contribute to tumorigenesis by disregulating critical target genes such as ones involved in apoptosis, proliferation and blocking differentiation or cell cycle exit.
[3] It arises when cerebellar granule neurone progenitor (GNP) cells fail to properly migrate and differentiate.
This SHH signalling pathway is crucial during early development and SSH is the major mitogen for GNP proliferation.
[3] Turcots's syndrome can give rise to MB as well, resulting from a mutated adenomatous polyposis coli (APC) gene (a member of the wingless (WNT signalling pathway).
miRNA libraries constructed from cloning and sequencing short RNAs derived from cultures of mouse embryonic stem cells have shown miR-92 to be expressed.
An miRNA that remains constant in its expression through these stages is proposed to have a role in regulating general aspects of cell physiology.
Also there are no mRNA markers that show consistent differential expression between tumours and normal tissues but profiling all of the miRNAs has proved much more informative with respect to cancer diagnosis and its developmental origins.
In one report, miRanda software found 300 different genes that have putative miR-92a binding sites conserved among Homo sapiens, Mus musculus, and Rattus norvegicus at the 3' UTR regions of their transcripts.
Deletions and loss of function to the SMN complex has been correlated with the neurodegenerative disease spinal muscular atrophy.
Although the over-all expression profiles were not significantly different the rank order of intensity of a few key small RNAs changed drastically enough to encourage attention and specific analysis.
91 miRNAs are present in human plasma[10] and it has been proposed that miR-92a along with other serum-typical miRs such as miR-638, are packaged inside exosomes that are secreted from cells.
Of the 26 miRNAs showing higher expression levels (in one of the mutant groups) against wild type mice, 9 of them were from the mir-17-92 cluster and its 2 paralogs.
In further studies with mice, an inhibitor of the SHH pathway (cyclopamine drug) was sufficient to reduce proliferation of tumour cells that had been infected with a retro virus encoding mir-17-92 (plus a GFP reporter).
[3] The miR-92 family is evolutionally conserved microRNAs,[14] and has an ortholog in Caenorhabditis elegans,[15] which has been extensively used as a model organism in the area of developmental biology.
Once nutritional conditions becomes favorable, the expression of mir-235 is downregulated by IIS pathway, and stem cells leave from quiescent state and resume the developmental program, such as self-renewal, migration and differentiation.
The modest number of miRNAs present in the genome and in specific profiling experiments allow for highly resolved patterns without overly complex data sets.
[4] 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 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.
[6] 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.