MicroRNAs in the Mammalian Gut Endocrine Lineage

MicroRNAs (miRNAs) are small noncoding RNA molecules that modulate gene expression at the posttranscriptional level. Numerous reports have elucidated the importance of miRNAs in the regulation of a wide array of biological processes including metabolism and energy homeostasis. miRNAs in the endocrine pancreas have been intensively studied over the last 15 years and linked to pancreatic islet development and function. In comparison, knowledge of miRNAs in gut endocrine cells, or enteroendocrine cells (EECs), is severely lacking. EECs have important roles in systemic energy homeostasis, are highly relevant to type 2 diabetes etiology, and may be critical to the mechanisms that underlie the rapid positive metabolic effects of bariatric surgery. Very recent studies reveal that several miRNAs are highly enriched in mature EECs and/or in intestinal stem cells that are primed to the EEC lineage. Moreover, functional experiments in enteroids/intestinal organoids suggest that some of these miRNAs may be important for the regulation of EEC differentiation and function. Another report has raised the possibility that EECs secrete miRNAs into circulation. These intriguing findings merit further investigation, particularly as it pertains to EEC miRNAs as novel therapeutic targets in type 2 diabetes and related diseases.