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TrkC‐miR2 regulates TGFβ signaling pathway through targeting of SMAD3 transcript

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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… Click to show full abstract

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 (TGFβ) 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 TGFβR1, TGFβR2, 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 TGFβ signaling pathway. Knowing its approved effect on Wnt signaling, TrkC‐miR2 here is introduced as a common regulator of both the Wnt and TGFβ 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.

Keywords: signaling pathway; mir2; trkc mir2; regulates tgf; tgf signaling

Journal Title: Journal of Cellular Biochemistry
Year Published: 2018

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