Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
J Cell Mol Med. 2021 Apr;25(7):3381-3390. doi: 10.1111/jcmm.16415. Epub 2021 Mar 6.
TrkC and NGFR neurotrophin receptors are associated with cell death, cancer and differentiation. TrkC-miR2, which is located in TrkC gene, is known to regulate Wnt signalling pathway, and its influence on other signalling pathways is under investigation. Here, through RT-qPCR, dual-luciferase assay and Western blotting we reveal that TrkC-miR2 targets NGFR. Overexpression of TrkC-miR2 also affected TrkA, TrkC, NFKB, BCL2 and Akt2 expressions involved in neurotrophin signalling pathway, and elevated survival rate of HEK293t and U87 cells was distinguished by flow cytometry and MTT assay. Consistently, an opposite expression correlation was obtained between TrkC-miR2 and NGFR or TrkC for the duration of NT2 differentiation. Meanwhile, TrkC-miR2 down-regulation attenuated NT2 differentiation into neural-like cells. Overall, here we present in silico and experimental evidence showing TrkC-miR2 as a new controller in regulation of neurotrophin signalling pathway.
TrkC 和 NGFR 神经营养因子受体与细胞死亡、癌症和分化有关。位于 TrkC 基因内的 TrkC-miR2 已知可调节 Wnt 信号通路,其对其他信号通路的影响正在研究中。在这里,通过 RT-qPCR、双荧光素酶报告基因检测和 Western blot,我们揭示了 TrkC-miR2 靶向 NGFR。TrkC-miR2 的过表达还影响了神经生长因子信号通路中涉及的 TrkA、TrkC、NFKB、BCL2 和 Akt2 的表达,并通过流式细胞术和 MTT 分析区分了 HEK293t 和 U87 细胞的存活率提高。一致地,在 NT2 分化过程中,我们获得了 TrkC-miR2 与 NGFR 或 TrkC 之间的相反表达相关性。同时,TrkC-miR2 的下调减弱了 NT2 分化为类神经细胞。总的来说,在这里,我们提供了基于计算机和实验的证据,表明 TrkC-miR2 是神经生长因子信号通路调节的新控制器。