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

Cellular and Molecular Life Sciences : CMLS
Sadat DokanehiifardSeyed J Mowla

Abstract

Tropomyosin receptor kinase C (TrkC) is involved in cell survival, apoptosis induction and tumorigenesis. We hypothesized that, similar to p75(NTR) 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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Citations

Aug 12, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Ali Jason SalehSeyed Javad Mowla
Oct 3, 2019·British Journal of Biomedical Science·S RamezaniS Alizadehsefat
Sep 29, 2017·Journal of Molecular Neuroscience : MN·Maryam HassanlouSeyed Javad Mowla
Mar 7, 2021·Journal of Cellular and Molecular Medicine·Sadat Dokaneheifard, Bahram M Soltani

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