Family
miR-92 is part of a large precursor sequence that forms a stem loop once transcribed into RNA. This long precursor sequence is a component of the mir-17-92 cluster which contains 6 additional mir precursor sequences: mir-17, mir-18a, mir-19a, mir-20a and mir19b-1. The components have related functions and also exist in their mature form as part of RNP complexes. The cluster is called Oncomir-1 because all members have been connected with inducing enhanced cell proliferation and suppression of apoptosis. Oncomir-1 has 2 paralogs, miR-106a-363 and mir-106b-25. These are located on different chromosomes and contain individual miRNAs that are highly similar to those encoded by the mir-17-92 cluster. Mir-92-1 for example, appears on the mir-17-92 cluster and mir-92-2 appears on the mir-106a-363 cluster. Because they have identical sequences in their mature form it is not always possible to establish which is prominent in a sample simply by sequencing the small RNA content. 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.
The miR-17-92 Cluster has been implicated in Medulloblastoma (MB) which is the most common paediatric malignant brain tumour. It arises when cerebellar granule neurone progenitor (GNP) cells fail to properly migrate and differentiate. MB can be induced by 2 inherited cancer syndromes, one of which is called the Gorlin syndrome and is caused by a mutated PATCHED(PTCH) gene. PTCH is the receptor for Sonic hedgehog (SHH). This SHH signalling pathway is crucial during early development and SSH is the major mitogen for GNP proliferation. 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). But only Gorlin syndrome and the SHH pathway is thought to incorporate the mode of action of the miR-17-92 cluster.
Read more about this topic: Mir-92 Micro RNA Precursor Family
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