Mir-199 microRNA precursor

The miR-199 microRNA precursor (homologous to miR-215), is a short non-coding RNA gene involved in gene regulation. miR-192 and miR-215 have now been predicted or experimentally confirmed in mouse, human and a further 21 other species. (MIPF0000040). microRNAs are transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give a ~22 nucleotide product. The mature products are thought to have regulatory roles through complementarity to mRNA.

Targets of miR-199
Using microarray and immunoblotting analyses it has been shown that miR-199a* targets the Met proto-oncogene.

MicroRNA hsa-miR-199a is a regulator of IκB kinase-β (IKKβ) expression.

Expression patterns of miR-199
Using TaqMan real-time quantitative PCR array methods, miRNA expression has been profiled. miR-199a, one of the most significantly overexpressed in invasive squamous cell carcinomas (ISCCs), was evaluated by transfecting cervical cancer cells (SiHa and ME-180) with anti-miR-199a oligonucleotides and the cell viability assessed. mirR-199a*, mir199a and mirR-199b were significantly overexpressed in ISCCs.

Comparative miRNA array led to the isolation of several Bone Morphogenic Protein 2 (BMP2)-responsive miRNAs. Among them, miR-199a* is of particular interest, because it was reported to be specifically expressed in the skeletal system.

Clinical relevance of miR-199
Alcoholic liver disease is a common medical consequence of chronic alcohol abuse. Activation of hypoxia-Inducible Factor-1α (HIF-1α) is an indicator of hypoxia. Endothelin-1 (ET-1) is a protein that constricts blood vessels and raises blood pressure. It has been shown that ethanol-induced miR-199 down-regulation may contribute to augmented HIF-1α and ET-1 expression.