title: Experimental verification of a conserved intronic microRNA located in the human TrkC gene with a cell type-dependent apoptotic function.
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.
authors.affiliation: Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Sadat
authors.initials: S
authors.lastname: Dokanehiifard
authors.forename: Bahram M
authors.initials: BM
authors.lastname: Soltani
authors.forename: Sepideh
authors.initials: S
authors.lastname: Parsi
authors.forename: Fahimeh
authors.initials: F
authors.lastname: Hosseini
authors.forename: Mohammad
authors.initials: M
authors.lastname: Javan
authors.forename: Seyed Javad
authors.initials: SJ
authors.lastname: Mowla
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001374:Azacitidine; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D019295:Computational Biology; D017931:DNA Primers / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D007438:Introns / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D051381:Rats; D020812:Receptor, trkC / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D035683:MicroRNAs; D020812:Receptor, trkC; D001374:Azacitidine