Mir-8/mir-141/mir-200 Micro RNA Precursor Family - Regulation of Insulin Signalling

Regulation of Insulin Signalling

miR-8, together with miR-200, has been identified as a regulator of insulin signalling in Drosophila fat body, the equivalent of liver and adipose tissue combined. This has led to speculation about further roles of these two members of this miRNA precursor family. mir-8 regulates body size in Drosophila in conjunction with its target USH, and the homolog miR-200 works in the same way with its respective target FOG2. Phosphoinositide 3-kinase (PI3K) is a kinase involved in a phosphorylation cascade which, once activated, works to enhance cell growth and proliferation. USH and FOG2 are able to inhibit PI3K activity through direct interaction with its regulatory subunits, dp60 and p85α respectively. This prevents the formation of an active PI3K complex. Elevated USH/F0G2 levels are observed in miR-8/200 null larvae, with a resultant downregulation in the PI3K activity of these larvae. In the presence of miR-8/200, insulin signalling in the fat body region is enhanced, and further cell size increases are seen with miR-8/200 overexpression. The effect of miR-8/200 on cell growth through insulin signalling has been found to vary in differing tissue types.