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Experimental verification of a conserved intronic microRNA located in the human TrkC gene with a cell type-dependent apoptotic function

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Abstract

Tropomyosin receptor kinase C (TrkC) is involved in cell survival, apoptosis induction and tumorigenesis. We hypothesized that, similar to p75NTR receptor, some of the diverse functions of TrkC could be mediated by a microRNA (miRNA) embedded within the gene. Here, we experimentally verified the expression and processing of two bioinformatically predicted miRNAs named TrkC-miR1-5p and TrkC-miR1-3p. Transfecting a DNA fragment corresponding to the TrkC-premir1 sequence in HEK293t cells caused ~300-fold elevation in the level of mature TrkC-miR1 and also a significant downregulation of its predicted target genes. Furthermore, endogenous TrkC-miR1 was detected in several cell lines and brain tumors confirming its endogenous generation. Furthermore, its orthologous miRNA was detected in developing rat brain. Accordingly, TrkC-miR1 expression was increased during the course of neural differentiation of NT2 cell, whereas its suppression attenuated NT2 differentiation. Consistent with opposite functions of TrkC, TrkC-miR1 overexpression promoted survival and apoptosis in U87 and HEK293t cell lines, respectively. In conclusion, our data report the discovery of a new miRNA with overlapping function to TrkC.

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Acknowledgments

The authors thank Dr. Masood Soleimani, Ali Jason Saleh, Leila Zare and Hamed Dabiri for their kind advices and technical supports. This work was supported by TMU, ISTI and INSF financial aids.

Conflict of interest

The authors declare that there are no conflicts of interest with any financial organization regarding the material discussed in the manuscript.

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Authors and Affiliations

  1. Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

    Sadat Dokanehiifard, Bahram M. Soltani, Sepideh Parsi, Fahimeh Hosseini & Seyed Javad Mowla

  2. Department of Physiology, School of Medicine, Tarbiat Modares University, Tehran, Iran

    Mohammad Javan

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  1. Sadat Dokanehiifard
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  2. Bahram M. Soltani
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  3. Sepideh Parsi
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  4. Fahimeh Hosseini
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Correspondence to Bahram M. Soltani.

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Dokanehiifard, S., Soltani, B.M., Parsi, S. et al. Experimental verification of a conserved intronic microRNA located in the human TrkC gene with a cell type-dependent apoptotic function. Cell. Mol. Life Sci. 72, 2613–2625 (2015). https://doi.org/10.1007/s00018-015-1868-4

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