Analysis of the expression, function, and evolution of miR-27 isoforms and their responses in metabolic processes

This study aimed to discuss the potential roles of isomiRs of miR-27 family in metabolisms associated with disease via analyses of their evolution, expression, and function. miR-27b-3p was relatively highly expressed in liver cancer samples compared to miR-27a-3p and miR-27-5p loci. The diversity of isomiRs in miR-27-3p locus is similar to that of miRNAs among homologous genes. IsomiRs exhibited variable expression across different cancer tissue types, and some of them were abnormally expressed in ob/ob mice. Further experimental validation indicated that the protein expression of metabolism-related proteins, including PEPCK, G6Pase, FAS, and CPT1A, were significantly suppressed when canonical miR-27b was transfected into AML-12 cells. In contrast, the expression of these proteins was only slightly inhibited by isomiR-27b-1 or isomiR-27b-2 after transfection into AML-12 cells. These observations support that isomiRs exhibiting sequence divergence are functional regulatory molecules, and that they may contribute to biological processes via coordinated interactions in regulatory networks.