MicroRNA let-7d is a target of cannabinoid CB1 receptor and controls cannabinoid signaling.

摘要: Cannabinoid CB1 receptor, the molecular target of endocannabinoids and cannabis active components, is one most abundant metabotropic receptors in brain. Cannabis widely used for both recreational medicinal purposes. Despite ever-growing fundamental roles microRNAs brain, possible connections between receptor are surprisingly unknown. Here, by using reporter gene constructs that express interaction sequences human SH-SY5Y neuroblastoma cells, we show activation enhances expression several microRNAs, including let-7d. This was confirmed measuring hsa-let-7d levels. Accordingly, knocking-down zebrafish reduced dre-let-7d levels, knocking-out mice decreased mmu-let-7d levels cortex, striatum hippocampus. Conversely, let-7d increased mRNA zebrafish, cells primary striatal neurons. Likewise, neurons chronically exposed to a cannabinoid or opioid agonist, let-7d-inhibiting sequence facilitated not only signaling but also cannabinoid/opioid cross-signaling. Taken together, these findings provide first evidence bidirectional link microRNA, namely let-7d, thus unveil new player complex process action.