Dokanehiifard Sadat, Soltani Bahram M
Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
J Cell Biochem. 2019 Feb;120(2):2634-2641. doi: 10.1002/jcb.27572. Epub 2018 Oct 10.
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.
神经营养因子受体TrkC在神经系统内外均发挥作用，对心血管形成的调节具有关键作用。最近，我们发现TrkC-miR2是位于TrkC基因中的一种新型微小RNA，它是Wnt信号通路的调节因子。在此，我们提供了大量证据表明TrkC-miR2也调节转化生长因子-β（TGFβ）信号通路。生物信息学研究预测SMAD3是TrkC-miR2真正的靶基因之一。定量逆转录PCR（RT-qPCR）、蛋白质免疫印迹分析和双荧光素酶测定分析证实SMAD3是TrkC-miR2的靶标。另一方面，在心脏球衍生细胞（CDC）中过表达TrkC-miR2，通过RT-qPCR检测发现TGFβR1、TGFβR2和SMAD7表达下调。同样，在CDC分化过程中以及人类胚胎干细胞分化为心肌细胞的过程中，均检测到TrkC-miR2与SMAD3基因表达呈负相关。总体而言，我们得出结论，TrkC-miR2下调SMAD3的表达并可能调节TGFβ信号通路。鉴于其对Wnt信号的已知作用，TrkC-miR2在此被视为Wnt和TGFβ信号通路的共同调节因子。因此，它可能是在结直肠癌和心脏发生等细胞过程中控制这两种信号通路的潜在关键因素。
