miR-204 has been proposed to modulate insulin expression in human pancreatic islets by regulating the expression of the MAFA transcript, and in turn insulin transcription. We investigated miR-204 expression in pancreatic endocrine tumors (PET), a panel of human tissues, tissues derived from pancreatic islet purification, and in induced pluripotent stem cells (iPSCs) differentiated towards a pancreatic endocrine phenotype by quantitative real time RT-PCR or droplet digital PCR (ddPCR). In addition, we evaluated the effect of miR-204 up- or down-regulation in purified human islets and in the EndoC-βH1 cell line, as an experimental model of human pancreatic β cells. Our results confirm that miR-204 was enriched in insulin producing PET, in β cells within healthy pancreatic islets, and highly expressed in EndoC-βH1 cells. Moreover, in iPSCs miR-204 increased stepwise upon stimulated differentiation to insulin producing cells. However, up- or down-regulation of miR-204 in human islets and in EndoC-βH1 cells resulted in modest and not significant changes of the MAFA and INS mRNAs measured by ddPCR or c-peptide release. Our data confirm the association of miR-204 with a β cell endocrine phenotype in human pancreatic islets, but do not support its direct role in regulating the levels of insulin mRNA through MAFA.
Marzinotto, I., Pellegrini, S., Brigatti, C., Nano, R., Melzi, R., Mercalli, A., Liberati, D., Sordi, V., Ferrari, M., Falconi, M., Doglioni, C., Ravassard, P., Piemonti, L., & Lampasona, V. (2017). miR-204 is associated with an endocrine phenotype in human pancreatic islets but does not regulate the insulin mRNA through MAFA. Scientific Reports, 7(2), . https://doi.org/10.1038/s41598-017-13622-7