microRNA overexpression in slow transit constipation leads to reduced NaV1.5 current and altered smooth muscle contractility.
Amelia MazzonePeter R StregeSimon J GibbonsConstanza AlcainoVikram JoshiAndrew J HaakDaniel J TschumperlinCheryl E BernardRobert R CimaDavid W LarsonHeidi K ChuaRondell P GrahamMona El RefaeyPeter J MohlerYujiro HayashiTamas OrdogStefan CalderPeng DuGianrico FarrugiaArthur BeyderPublished in: Gut (2019)
A small group of miRNAs is upregulated in STC, and many of these miRNAs target the SCN5A-encoded Na+ channel NaV1.5. Within this set, a novel NaV1.5 regulator, let-7f, resulted in decreased NaV1.5 expression, current density and reduced motility of GI smooth muscle. These results suggest NaV1.5 and miRNAs as novel diagnostic and potential therapeutic targets in STC.