TrkC-miR2 regulates TGF signaling pathway through targeting of SMAD3 transcript

TrkC, neurotrophin receptor, functions inside and outside of the nervous system and has a crucial effect on the regulation of cardiovascular formation. Recently, we introduced TrkC-miR2 as a novel microRNA located in TrkC gene, which is a regulator of the Wnt signaling pathway. Here, we presented a lot of evidence showing that TrkC-miR2 also regulates the transforming growth factor-beta (TGF) signaling pathway. Bioinformatics studies predicted SMAD3 as one of the bona fide TrkC-miR2 target genes. Quantitative reverse transcription PCR (RT-qPCR), Western blot analysis, and dual luciferase assay analysis confirmed that SMAD3 is targeted by TrkC-miR2. On the other hand, overexpression of TrkC-miR2 in cardiosphere-derived cells (CDCs) rendered downregulation of TGFR1, TGFR2, and SMAD7 detected by RT-qPCR. Consistently, an inverse correlation of expression between TrkC-miR2 and SMAD3 genes was detected during the course of CDC differentiation, and also during the course of human embryonic stem cells differentiation to cardiomyocytes. Overall, we conclude that TrkC-miR2 downregulates the expression of SMAD3 and potentially regulates the TGF signaling pathway. Knowing its approved effect on Wnt signaling, TrkC-miR2 here is introduced as a common regulator of both the Wnt and TGF signaling pathways. Therefore, it may be a potential key element in controlling both of these signaling pathways in cell processes like colorectal cancer and cardiogenesis.