Santina Venuto1, Stefano Castellana2, Maria Monti3, Irene Appolloni4, Caterina Fusilli5, Carmela Fusco6, Piero Pucci7, Paolo Malatesta8, Tommaso Mazza9, Giuseppe Merla10, Lucia Micale11. 1. Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale Padre Pio, 71013, San Giovanni Rotondo, Foggia, Italy; Experimental and Regenerative Medicine, University of Foggia, Via A. Gramsci, 89/91, 71122, Foggia, Italy. Electronic address: s.venuto@operapadrepio.it. 2. Bioinformatics Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale Padre Pio, 71013, San Giovanni Rotondo, Foggia, Italy. Electronic address: s.castellana@css-mendel.it. 3. CEINGE Advanced Biotechnology, Department of Chemical Sciences, Federico II University, Via Gaetano Salvatore, 486, 80145, Napoli, Italy. Electronic address: montimar@unina.it. 4. U.O. Medicina Rigenerativa Ospedale Policlinico San Martino, Largo R. Benzi 10, 16132 Genova, Italy. 5. Bioinformatics Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale Padre Pio, 71013, San Giovanni Rotondo, Foggia, Italy. Electronic address: c.fusilli@css-mendel.it. 6. Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale Padre Pio, 71013, San Giovanni Rotondo, Foggia, Italy. Electronic address: c.fusco@operapadrepio.it. 7. CEINGE Advanced Biotechnology, Department of Chemical Sciences, Federico II University, Via Gaetano Salvatore, 486, 80145, Napoli, Italy. Electronic address: pietro.pucci@unina.it. 8. U.O. Medicina Rigenerativa Ospedale Policlinico San Martino, Largo R. Benzi 10, 16132 Genova, Italy; Department of Experimental Medicine (DiMES), University of Genova, Via Leon Battista Alberti, 2, 16132 Genova, Italy. Electronic address: paolo.malatesta@unige.it. 9. Bioinformatics Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale Padre Pio, 71013, San Giovanni Rotondo, Foggia, Italy. Electronic address: t.mazza@operapadrepio.it. 10. Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale Padre Pio, 71013, San Giovanni Rotondo, Foggia, Italy. Electronic address: g.merla@operapadrepio.it. 11. Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale Padre Pio, 71013, San Giovanni Rotondo, Foggia, Italy. Electronic address: l.micale@operapadrepio.it.
Abstract
BACKGROUND: We recently reported TRIM8, encoding an E3 ubiquitin ligase, as a gene aberrantly expressed in glioblastoma whose expression suppresses cell growth and induces a significant reduction of clonogenic potential in glioblastoma cell lines. METHODS: we provided novel insights on TRIM8 functions by profiling the transcriptome of TRIM8-expressing primary mouse embryonal neural stem cells by RNA-sequencing and bioinformatic analysis. Functional analysis including luciferase assay, western blot, PCR arrays, Real time quantitative PCR were performed to validate the transcriptomic data. RESULTS: Our study identified enriched pathways related to the neurotransmission and to the central nervous system (CNS) functions, including axonal guidance, GABA receptor, Ephrin B, synaptic long-term potentiation/depression, and glutamate receptor signalling pathways. Finally, we provided additional evidence about the existence of a functional interactive crosstalk between TRIM8 and STAT3. CONCLUSIONS: Our results substantiate the role of TRIM8 in the brain functions through the dysregulation of genes involved in different CNS-related pathways, including JAK-STAT. GENERAL SIGNIFICANCE: This study provides novel insights on the physiological TRIM8 function by profiling for the first time the primary Neural Stem Cell over-expressing TRIM8 by using RNA-Sequencing methodology.
BACKGROUND: We recently reported TRIM8, encoding an E3 ubiquitin ligase, as a gene aberrantly expressed in glioblastoma whose expression suppresses cell growth and induces a significant reduction of clonogenic potential in glioblastoma cell lines. METHODS: we provided novel insights on TRIM8 functions by profiling the transcriptome of TRIM8-expressing primary mouse embryonal neural stem cells by RNA-sequencing and bioinformatic analysis. Functional analysis including luciferase assay, western blot, PCR arrays, Real time quantitative PCR were performed to validate the transcriptomic data. RESULTS: Our study identified enriched pathways related to the neurotransmission and to the central nervous system (CNS) functions, including axonal guidance, GABA receptor, Ephrin B, synaptic long-term potentiation/depression, and glutamate receptor signalling pathways. Finally, we provided additional evidence about the existence of a functional interactive crosstalk between TRIM8 and STAT3. CONCLUSIONS: Our results substantiate the role of TRIM8 in the brain functions through the dysregulation of genes involved in different CNS-related pathways, including JAK-STAT. GENERAL SIGNIFICANCE: This study provides novel insights on the physiological TRIM8 function by profiling for the first time the primary Neural Stem Cell over-expressing TRIM8 by using RNA-Sequencing methodology.
Authors: Jie Yang; John R Horton; Jia Li; Yun Huang; Xing Zhang; Robert M Blumenthal; Xiaodong Cheng Journal: Nucleic Acids Res Date: 2019-09-19 Impact factor: 16.971